Journal articles on the topic 'Sheep Fetuses'
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1
Salehi, Mitra, Hosein Nezami, and Hamid Reza Niazkar. "Investigation of Toxoplasma gondii Infection in Aborted Fetuses of Sheep Using PCR: A Study in North Khorasan Province, Iran." Veterinary Medicine International 2020 (June 20, 2020): 1–5. http://dx.doi.org/10.1155/2020/7913912.
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Toxoplasma gondii is a zoonotic obligate intracellular protozoan parasite that infects warm-blooded animals as well as humans worldwide. The purpose of this study was to delineate the prevalence of Toxoplasma infection in aborted fetuses of sheep in North Khorasan province, Iran. Three hundred and ninety-nine samples of the liver (133 samples), placenta (133 samples), and brain (133 samples) from 133 aborted fetuses of sheep were collected from 2015 to 2017. The ages of aborted fetuses were higher than 120 days’ gestational age in this study. According to the samples, sixteen out of 133 aborted fetuses of sheep were infected with T. gondii. Toxoplasma DNA was found in the placenta (68.75%) and liver (31.25%) samples of infected fetuses using the PCR method. The highest and lowest rates of Toxoplasma infection were observed during 2016 and 2017, respectively. Shirvan and Faruj provinces were recognized as the two most infected districts among others. There was a significant difference between the year and abortion rate in sheep due to infection by the Toxoplasma parasite (P<0.05). Furthermore, no significant difference between the prevalence of T. gondii infection and aborted fetuses was seen (P>0.05) in different areas. According to the present study, T. gondii infection can be one of the causes of fetus abortion of sheep in North Khorasan province, Iran.
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Ceccarelli, P., V. Pedini, and A. M. Gargiulo. "Enteroendocrine cells in sheep fetuses." Small Ruminant Research 6, no. 1-2 (October 1991): 85–93. http://dx.doi.org/10.1016/0921-4488(91)90011-e.
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Houghton, Pamela E., Thomas J. McDonald, and John R. G. Challis. "Ontogeny of the insulin response to glucose in fetal and adult sheep." Canadian Journal of Physiology and Pharmacology 67, no. 10 (October 1, 1989): 1288–93. http://dx.doi.org/10.1139/y89-205.
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The purpose of the present experiments was to examine in sheep whether the fetal insulin response to glucose was present by day 110 (d110) of pregnancy and whether the magnitude of the fetal insulin response changed between d110 and d145 (term). We also compared the responses observed in fetuses to those of adult nonpregnant sheep. Basal concentrations of glucose measured in plasma collected from the fetal femoral artery rose progressively between d110 and d145 of gestation, but did not attain the plasma glucose concentrations measured in adult sheep. Peak glucose concentrations in fetuses were achieved 10 min following the bolus injection of glucose (0.8 g/kg estimated fetal body weight) into the fetal femoral vein, and peak values increased with gestational age. Significantly higher peak glucose concentrations were achieved in adult sheep. The concentration of insulin rose rapidly in fetuses at d110, and a similar time course of insulin release in plasma was seen at all gestational ages. The peak plasma insulin concentrations were achieved at 20 min and were significantly greater in older (d140–145) than younger (d125–130) fetuses (p < 0.05). Peak insulin values in fetuses were much less than in adult sheep. In adult sheep glucose and insulin concentrations remained elevated at 120 min following the injection of glucose, whereas in the fetus the concentration of insulin had returned to preinjection values by 60 min. The insulin/glucose ratio did not change in fetal lambs over the last one third of gestation and was not different from the adult sheep. We conclude that (1) the fetal insulin response to an acute glucose load is present by d110 of gestation, and (2) the ratio of insulin released per unit glucose elevation did not change in fetal sheep over the last one third of gestation, nor between fetal and adult sheep.Key words: glucose, insulin, fetal sheep.
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Iwamoto, H. S., T. Kaufman, L. C. Keil, and A. M. Rudolph. "Responses to acute hypoxemia in fetal sheep at 0.6-0.7 gestation." American Journal of Physiology-Heart and Circulatory Physiology 256, no. 3 (March 1, 1989): H613—H620. http://dx.doi.org/10.1152/ajpheart.1989.256.3.h613.
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A majority of previous studies of fetal responses to acute hypoxemia has focused on the response of the sheep fetus greater than 120 days of gestation when many regulatory systems have been established. To assess the response of younger, less well-developed fetuses, we exposed two groups of fetal sheep (I, 84-91 days; II, 97-99 days gestational age) to acute hypoxemia by giving the ewe a gas mixture containing 9% O2 to breathe. We decreased descending aortic PO2 in both groups of fetuses [I, 24 +/- 6 to 14 +/- 3 (SD) Torr; II, 23 +/- 3 to 12 +/- 4 Torr] by a degree similar to that achieved in previous studies of fetuses greater than 120 days of gestation. Mean arterial blood pressure (I, 31 +/- 6; II, 40 +/- 3 Torr) did not change significantly from control values, and heart rate (I, 224 +/- 27; II, 203 +/- 16 beats/min) increased significantly in group II fetuses with hypoxemia. In group I and II fetuses, as in older fetuses, cerebral, myocardial, and adrenal blood flows, measured by the microsphere technique, increased, and pulmonary blood flow decreased. These responses mature early and are likely local vascular responses to decreases in oxygen content. Combined ventricular output and umbilical-placental blood flow decreased significantly in both groups. Unlike the response of the fetus greater than 120 days, acute hypoxemia did not decrease blood flow to the musculoskeletal and cutaneous circulations (group I only), gastrointestinal, or renal circulations.(ABSTRACT TRUNCATED AT 250 WORDS)
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Owens, J. A., J. Falconer, and J. S. Robinson. "Effect of restriction of placental growth on umbilical and uterine blood flows." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 250, no. 3 (March 1, 1986): R427—R434. http://dx.doi.org/10.1152/ajpregu.1986.250.3.r427.
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Endometrial caruncles were excised from sheep (caruncle sheep) before pregnancy. The effect of this on umbilical and uterine blood flows in a subsequent pregnancy was examined. Thirteen caruncle and twelve control sheep with indwelling vascular catheters were studied at 121 and 130 days pregnancy. In caruncle sheep, fetal, placental, and total uterine content weights were significantly lower than in control sheep. Six caruncle sheep carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses) and seven carried small fetuses (weight greater than +/- 2 SD below mean weight for control fetuses). Mean weights of placentas in these groups were 0.290 +/- 0.067 and 0.156 +/- 0.069 kg, respectively, compared with 0.459 +/- 0.157 kg in control sheep. In small caruncle fetuses, umbilical and uterine blood flows and placental antipyrine clearance were significantly lower than in controls at 121 and 130 days gestation. Only umbilical blood flow was reduced in normal-sized caruncle fetuses. Umbilical blood flow and placental antipyrine clearance increased with gestational age in control sheep but not in sheep with normal-sized or small caruncle fetuses. In all sheep, umbilical and uterine blood flows and antipyrine clearance correlated with placental weight. Umbilical blood flow per kilogram of placenta but not uterine blood flow per kilogram of placenta correlated inversely with placental weight. Fetal weight at 130 days generally correlated with placental weight, umbilical and uterine blood flows, and antipyrine clearance in a curvilinear fashion such that fetal weight was not greatly restricted until these variables were less than or equal to 65% of control values.
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Raff, H., and C. E. Wood. "Effect of age and blood pressure on the heart rate, vasopressin, and renin response to hypoxia in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 263, no. 4 (October 1, 1992): R880—R884. http://dx.doi.org/10.1152/ajpregu.1992.263.4.r880.
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The purpose of these studies was to determine whether attenuating the increase in arterial and central venous pressure (CVP) during acute hypoxia can augment the renin and arginine vasopressin (AVP) responses to isocapnic hypoxia in chronically instrumented sheep fetuses. Young (122 +/- 2 days; n = 7) and old (133 +/- 1 days, n = 7) fetuses were exposed to hypoxemia (arterial PO2 = approximately 12-13 Torr) without and with attenuation of the increase in mean arterial pressure (MAP) and CVP with the simultaneous infusion of sodium nitroprusside (NP). NP did not attenuate the bradycardia induced by hypoxia. Plasma renin activity did not increase with hypoxia even when the potentially inhibitory effect of increased MAP and CVP was attenuated with NP. The AVP response to hypoxia was greater in the old fetuses. Furthermore, NP did augment the AVP response to hypoxia in the young but not old fetuses. We conclude that increases in MAP and CVP (i.e., baroreceptor input) do not influence the decrease in heart rate and lack of renin responses to acute hypoxia in the sheep fetus and that increased MAP and CVP seems to restrain the AVP response to hypoxia in younger sheep fetuses.
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Lakhdir, Farahaba R., Haiyan Tong, and Charles E. Wood. "Baroreceptor and prostanoid control of fetal renal cortical blood flow and plasma renin activity." Reproduction, Fertility and Development 13, no. 3 (2001): 119. http://dx.doi.org/10.1071/rd00101.
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Renal function in the fetus is important for maintenance of fetal fluid and electrolyte balance. This study was performed to test the role of prostaglandins and their interaction with arterial baroreceptors and chemoreceptors in the control of renal cortical blood flow during hypotension produced by vena caval obstruction in late-gestation fetal sheep. We studied 18 time-dated, chronically catheterized, fetal sheep (124–136 days gestation). Fetuses were either studied intact (n = 11) or sinoaortic denervated (n = 7), and each fetus was studied twice, with and without pretreatment with indomethacin (0.2 mg kg –1 , i.v.). Each fetus was subjected to hypotension caused by vena caval obstruction for 10 min. Before hypotension, renal cortical blood flow was higher in the vehicle-treated sinoaortic denervated fetuses than in vehicle-treated intact fetuses. The increased renal cortical blood flow observed in the sinoaortic denervated fetuses was counteracted by indomethacin, so that the difference between sinoaortic denervated and intact fetuses was eliminated after indomethacin treatment. Hypotension decreased renal blood flow equally in all groups. Plasma renin activity was increased in response to hypotension in the intact fetuses, but not in the sinoaortic denervated fetuses. Indomethacin treatment, by itself, did not alter plasma renin activity. It is concluded that both arterial baroreceptors and prostanoids influence renal blood flow. Further, renin secretion is influenced by arterial baroreceptors and chemoreceptors and there is no apparent modulatory effect of prostanoids on the baroreflex control of renin secretion.
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Forhead, AJ, and AL Fowden. "Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term." Journal of Endocrinology 173, no. 1 (April 1, 2002): 143–50. http://dx.doi.org/10.1677/joe.0.1730143.
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In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.
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Jensen, EC, JE Harding, MK Bauer, and PD Gluckman. "Metabolic effects of IGF-I in the growth retarded fetal sheep." Journal of Endocrinology 161, no. 3 (June 1, 1999): 485–94. http://dx.doi.org/10.1677/joe.0.1610485.
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It has been shown that IGF-I has an anabolic effect in the normal fetus. However, there is evidence to suggest that there may be IGF-I resistance in the growth retarded fetus. Therefore, we investigated the effects of acute IGF-I infusion to chronically catheterised fetal sheep. At 128 days gestation, fetuses underwent a 4 h infusion of IGF-I (50 microg/kg/h). Three groups of animals were studied. Nine normally grown fetuses were studied as controls. Embolised animals (n=8) received microspheres into the uterine vasculature, and animals with spontaneous intra-uterine growth retardation (IUGR animals) (n=6) were fetuses found at post mortem to be spontaneously growth restricted. The effects of IGF-I infusion on feto-placental carbohydrate and protein metabolism were similar in our control group to previous similar experiments. IGF-I infusion decreased fetal blood glucose, oxygen, urea and amino-nitrogen concentrations, and inhibited placental lactate production. The same fetal blood metabolite concentrations also fell during IGF-I infusion in the embolised fetuses, but the effect on placental lactate production was not seen. The only effect of IGF-I infusion in the spontaneous IUGR animals was a fall in fetal blood amino-nitrogen concentrations. We conclude that fetal IGF-I infusion does not have the same anabolic effects in the growth retarded fetus as the normal fetus. In addition, the effects of IGF-I were different in the two growth retarded groups. Our data support previous evidence that the growth retarded fetus has altered IGF-I sensitivity, and this may vary depending on the cause, severity and duration of growth retardation.
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S. M, Amin F. A. "Prenatal Study of Testes Growth and Histological Development 1- Fetal Sheep." Iraqi Journal of Veterinary Medicine 34, no. 1 (June 30, 2010): 191–200. http://dx.doi.org/10.30539/iraqijvm.v34i1.679.
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This study was conducted on 200 samples of females Karadi sheep genitalia contains 207 fetuses . These samples were collected from slaughter house in Sulaimani reigion during the period from June 2007 to the end of May 2008. Sheep genitalia consisted of 193(96.5%) single and 7(3.5%) twin fetuses, amonge them 122 (58.92%)and 84(41.06) were in the right and left horns ,respectively. The genitalia that contain fetuses with clear external sex organs was 141, of these 74 male and 67 female fetuses different Crown Rump Length (CRL), while 66 fetus their sex could diagnosis after abdominal opened. The results showed the weight of the fetal body and testes as well as the length of scrotum were increased with an increasing of the fetal CRL. The appearance of the fetal testes in the inguinal ring was when CRL=22cm .80 day; in the scrotum 32 cm. 100 day ; Histological sections of the fetal testes were showed the density of fibroblast layer and connective tissue capsules as well as the appearance of seminiferous tubules containing a few spermatogonia cells and small sertoli and leydig cells at early CRL=10 cm 55 day; , with increasing fetal CRL the seminiferous tubules filled with different types of spermatogonia and spermatocytes cells as well as increasing in the number of sertoli and leydig cells were recorded at CRL= 20.3 cm. 75 days; While the metamorphosis spermatid were seen at CRL=24cm . 80-85 day; Conclusions : Fetal sheep seminiferous tubules early in gestation contain different types of spermatognium and spermatocyte cells appear in the testes after 50 days, and metamorphosis spermatid were seen after 80 days of intra uterine life no sperm was seen in fetuse testes.. It was concluded that the fetal testes in early gestation could be secreted testosterone which lead to increases in fetal testes development and growth of the germinal and somatic cells
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Hasan, S. U., D. S. Lee, D. A. Gibson, B. J. Nowaczyk, D. B. Cates, D. S. Sitar, C. Pinsky, and H. Rigatto. "Effect of morphine on breathing and behavior in fetal sheep." Journal of Applied Physiology 64, no. 5 (May 1, 1988): 2058–65. http://dx.doi.org/10.1152/jappl.1988.64.5.2058.
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To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116–141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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Karamlou, Tara, George D. Giraud, Donogh McKeogh, Sonnet S. Jonker, Irving Shen, Ross M. Ungerleider, and Kent L. Thornburg. "Right ventricular remodeling in response to volume overload in fetal sheep." American Journal of Physiology-Heart and Circulatory Physiology 316, no. 5 (May 1, 2019): H985—H991. http://dx.doi.org/10.1152/ajpheart.00439.2018.
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The fetal myocardium is known to be sensitive to hemodynamic load, responding to systolic overload with cellular hypertrophy, proliferation, and accelerated maturation. However, the fetal cardiac growth response to primary volume overload is unknown. We hypothesized that increased venous return would stimulate fetal cardiomyocyte proliferation and terminal differentiation, particularly in the right ventricle (RV). Vascular catheters and pulmonary artery flow probes were implanted in 16 late-gestation fetal sheep: a right carotid artery-jugular vein (AV) fistula was surgically created in nine fetuses, and sham operations were performed on seven fetuses. Instrumented fetuses were studied for 1 wk before hearts were dissected for component analysis or cardiomyocyte dispersion for cellular measurements. Within 1 day of AV fistula creation, RV output was 20% higher in experimental than sham fetuses ( P < 0.0001). Circulating atrial natriuretic peptide levels were elevated fivefold in fetuses with an AV fistula ( P < 0.002). On the terminal day, RV-to-body weight ratios were 35% higher in the AV fistula group ( P < 0.05). Both left ventricular and RV cardiomyocytes grew longer in fetuses with an AV fistula ( P < 0.02). Cell cycle activity was depressed by >50% [significant in left ventricle ( P < 0.02), but not RV ( P < 0.054)]. Rates of terminal differentiation were unchanged. Based on these studies, we speculate that atrial natriuretic peptide suppressed fetal cardiomyocyte cell cycle activity. Unlike systolic overload, fetal diastolic load appears to drive myocyte enlargement, but not cardiomyocyte proliferation or maturation. These changes could predispose to RV dysfunction later in life. NEW & NOTEWORTHY Adaptation of the fetal heart to changes in cardiac load allows the fetus to maintain adequate blood flow to its systemic and placental circulations, which is necessary for the well-being of the fetus. Addition of arterial-venous fistula flow to existing venous return increased right ventricular stroke volume and output. The fetal heart compensated by cardiomyocyte elongation without accelerated cellular maturation, while cardiomyocyte proliferation decreased. Even transient volume overload in utero alters myocardial structure and cardiomyocyte endowment.
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Beanland, C., C. Browne, R. Young, J. Owens, P. Walton, and G. Thorburn. "Fetal plasma insulin-like growth factor-binding protein-3 concentrations are elevated following bilateral nephrectomy in fetal sheep." Reproduction, Fertility and Development 7, no. 3 (1995): 345. http://dx.doi.org/10.1071/rd9950345.
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Insulin-like growth factors mediate many of the effects of growth hormone and are important in the regulation of growth, especially in the fetus where growth is less dependent on circulating growth hormone. In the ovine fetus, insulin-like growth factor-I (IGF-I) is bound mainly to the low molecular weight insulin-like growth factor-binding proteins (IGFBP), IGFBP-1 and IGFBP-2, with little binding to IGFBP-3 until near term at 147 days gestation. To determine if there was any difference in plasma IGF-I and IGFBP-3 concentrations in growth-retarded fetal sheep with altered renal status, concentrations were measured by specific radioimmunoassay from bilaterally nephrectomized fetal sheep between Days 113 and 135 gestation. Plasma IGFBP-3 concentrations were significantly (P < 0.001) increased in bilaterally nephrectomized fetuses (4.19 +/- 0.19 micrograms mL-1, n = 7) compared with control fetuses (2.33 +/- 0.10 micrograms mL-1, n = 7). There was no change in plasma IGFBP-3 concentration with gestational age in either experimental group. Maternal plasma IGFBP-3 concentrations did not differ between the bilateral nephrectomy group (3.11 +/- 0.09 micrograms mL-1, n = 7) and the control group (3.25 +/- 0.11 micrograms mL-1, n = 7) and showed no change within groups over the experimental period. Total plasma IGF-I concentrations in bilaterally nephrectomized fetuses and ewes were similar to those in control fetuses and ewes. The results indicate that the profile of IGF binding in fetal plasma is altered in the anephric fetal sheep. In nephrectomized fetal sheep, increased IGFBP-3 concentrations, and therefore increased IGF-binding capacity in fetal plasma, may have contributed to a decrease in free IGF in plasma and decreased IGF-I bioactivity. This would provide a possible mechanism for the growth retardation reported in bilaterally nephrectomized fetal sheep.
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Davis, Melissa A., Leticia E. Camacho, Miranda J. Anderson, Nathan R. Steffens, Alexander L. Pendleton, Amy C. Kelly, and Sean W. Limesand. "Chronically elevated norepinephrine concentrations lower glucose uptake in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 319, no. 3 (September 1, 2020): R255—R263. http://dx.doi.org/10.1152/ajpregu.00365.2019.
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Fetal conditions associated with placental insufficiency and intrauterine growth restriction (IUGR) chronically elevate plasma norepinephrine (NE) concentrations. Our objective was to evaluate the effects of chronically elevated NE on insulin-stimulated glucose metabolism in normally grown, non-IUGR fetal sheep, which are independent of other IUGR-related reductions in nutrients and oxygen availability. After surgical placement of catheters, near-term fetuses received either a saline (control) or NE intravenous infusion with controlled euglycemia. In NE fetuses, plasma NE concentrations were 5.5-fold greater than controls, and fetal euglycemia was maintained with a maternal insulin infusion. Insulin secretion was blunted in NE fetuses during an intravenous glucose tolerance test. Weight-specific fluxes for glucose were measured during a euinsulinemic-euglycemic clamp (EEC) and a hyperinsulinemic-euglycemic clamp (HEC). Plasma glucose and insulin concentrations were not different between groups within each clamp, but insulin concentrations increased 10-fold between the EEC and the HEC. During the EEC, rates of glucose uptake (umbilical uptake + exogenous infusion) and glucose utilization were 47% and 35% lower ( P < 0.05) in NE fetuses compared with controls. During the HEC, rates of glucose uptake were 28% lower ( P < 0.05) in NE fetuses than controls. Glucose production was undetectable in either group, and glucose oxidation was unaffected by the NE infusion. These findings indicate that chronic exposure to high plasma NE concentrations lowers rates of net glucose uptake in the fetus without affecting glucose oxidation rates or initiating endogenous glucose production. Lower fetal glucose uptake was independent of insulin, which indicates insulin resistance as a consequence of chronically elevated NE.
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Davis, L. E., and A. R. Hohimer. "Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 6 (December 1, 1991): R1542—R1548. http://dx.doi.org/10.1152/ajpregu.1991.261.6.r1542.
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To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure.
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Brown, Laura D., Stephanie R. Wesolowski, Jenai Kailey, Stephanie Bourque, Averi Wilson, Sasha E. Andrews, William W. Hay, and Paul J. Rozance. "Chronic Hyperinsulinemia Increases Myoblast Proliferation in Fetal Sheep Skeletal Muscle." Endocrinology 157, no. 6 (April 6, 2016): 2447–60. http://dx.doi.org/10.1210/en.2015-1744.
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Insulin is an important fetal growth factor. However, chronic experimental hyperinsulinemia in the fetus fails to accelerate linear and lean mass growth beyond normal rates. Mechanisms preventing accelerated lean mass accretion during hyperinsulinemia are unknown. To address potential mechanisms, late-gestation fetal sheep were infused with iv insulin and glucose to produce euglycemic hyperinsulinemia (INS) or saline for 7–9 days. Fetal substrate uptake and protein metabolic rates were measured. INS fetuses had 1.5-fold higher insulin concentrations (P < .0001) and equivalent glucose concentrations. INS fetuses had 20% more Pax7+ nuclei in the biceps femoris, which indicates the potential for hyperinsulinemia to increase the number of myoblasts within late-gestation fetal skeletal muscle. Additionally, the percentage of Pax7+ myoblasts that expressed Ki-67 was 1.3-fold higher and expression of myogenic regulatory factors was 50% lower in INS fetuses (MYF5 and MYOG [myogenin], P < .005), which indicates a shift toward myoblast proliferation over differentiation. There were no differences for fetal body, organ, or muscle weights, although INS placentas weighed 28% less (P < .05). Protein synthesis and accretion rates did not change in INS fetuses, nor did fiber muscle size. Essential amino acid concentrations were lower in the INS group (P < .05) except for tryptophan. Umbilical blood flow, net total amino acids, and O2 uptakes rates did not differ between groups. Arterial O2 content was 33% lower (P < .005) and norepinephrine was 100% higher in the INS fetuses (P < .01), all of which are factors that may counteract fetal protein accretion during hyperinsulinemia despite an increase in myoblast proliferation.
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Limesand, Sean W., Paul J. Rozance, Laura D. Brown, and William W. Hay. "Effects of chronic hypoglycemia and euglycemic correction on lysine metabolism in fetal sheep." American Journal of Physiology-Endocrinology and Metabolism 296, no. 4 (April 2009): E879—E887. http://dx.doi.org/10.1152/ajpendo.90832.2008.
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In this study, we determined rates of lysine metabolism in fetal sheep during chronic hypoglycemia and following euglycemic recovery and compared results with normal, age-matched euglycemic control fetuses to explain the adaptive response of protein metabolism to low glucose concentrations. Restriction of the maternal glucose supply to the fetus lowered the net rates of fetal (umbilical) glucose (42%) and lactate (36%) uptake, causing compensatory alterations in fetal lysine metabolism. The plasma lysine concentration was 1.9-fold greater in hypoglycemic compared with control fetuses, but the rate of fetal (umbilical) lysine uptake was not different. In the hypoglycemic fetuses, the lysine disposal rate also was higher than in control fetuses due to greater rates of lysine flux back into the placenta and into fetal tissue. The rate of CO2 excretion from lysine decarboxylation was 2.4-fold higher in hypoglycemic than control fetuses, indicating greater rates of lysine oxidative metabolism during chronic hypoglycemia. No differences were detected for rates of fetal protein accretion or synthesis between hypoglycemic and control groups, although there was a significant increase in the rate of protein breakdown ( P < 0.05) in the hypoglycemic fetuses, indicating small changes in each rate. This was supported by elevated muscle specific ubiquitin ligases and greater concentrations of 4E-BP1. Euglycemic recovery after chronic hypoglycemia normalized all fluxes and actually lowered the rate of lysine decarboxylation compared with control fetuses ( P < 0.05). These results indicate that chronic hypoglycemia increases net protein breakdown and lysine oxidative metabolism, both of which contribute to slower rates of fetal growth over time. Furthermore, euglycemic correction for 5 days returns lysine fluxes to normal and causes an overcorrection of lysine oxidation.
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Nagao, Y., T. Abe, A. Hara, B. Sarentonglaga, M. Yamaguchi, K. Ogata, R. Fukumori, and Y. Hanazono. "334 FACTORS AFFECTING HEMATOPOIETIC ENGRAFTMENT OF MONKEY EMBRYONIC STEM CELLS IN SHEEP FETUSES." Reproduction, Fertility and Development 27, no. 1 (2015): 255. http://dx.doi.org/10.1071/rdv27n1ab334.
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Previously, we generated monkey/sheep haematopoietic chimeras by in utero transplantation (IUT) of monkey embryonic stem (ES); however, the factors that control how the ES cells successfully engraft and differentiate into haematopoietic tissue in sheep fetuses remain uncertain. Here, we examined factors that might influence donor cells and recipient sheep and affect successful ES cell engraftment. We transplanted either undifferentiated monkey ES cells or ES-derived cells at an early haematopoietic differentiation stage into sheep fetuses. The latter cells were allowed to differentiate by culturing on OP9 cell layers for 6 days. Cells were transplanted into the liver or subcutaneous tissue of recipient sheep fetuses at 43 to 50 or 51 to 67 days of gestation (full term = 147 days) using ultrasound to identify the site for transplantation. After birth, monkey haematopoietic engraftment in the bone marrow was analysed in 40 lambs using colony-PCR with cells grown in methylcellulose in the presence of defined cytokines; teratoma formation was analysed by biopsy and immunohistochemistry. We found that haematopoietic engraftment was only observed when ES-derived cells at the early differentiation stage were transplanted into fetal livers at 51 to 67 days of gestation (6/9). However, teratoma formation with mature monkey tissue structures was only observed following transplantation of undifferentiated ES cells into fetal subcutaneous tissues at 43 to 50 days of gestation (4/6), but that was not observed when both types of cells were transplanted into the liver (0/18) or at 51 to 67 days of gestation (0/24). These results demonstrate that the differentiation status of the donor cells, the transplantation site, and the age of the fetus at transplantation are important factors in engraftment and differentiation into haematopoietic tissue or teratoma formation in sheep fetuses.
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Gleason, Christine A., Roderick Robinson, Andrew P. Harris, Dennis E. Mayock, and Richard J. Traystman. "Cerebrovascular effects of intravenous dopamine infusions in fetal sheep." Journal of Applied Physiology 92, no. 2 (February 1, 2002): 717–24. http://dx.doi.org/10.1152/japplphysiol.00600.2001.
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Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 μg · kg−1 · min−1. In preterm fetuses, MAP increased only at 75 μg · kg−1 · min−1 (25 ± 5%), whereas in near-term fetuses MAP increased at 25 μg · kg−1 · min−1 (28 ± 4%) and further at 75 μg · kg−1 · min−1 (51 ± 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 μg · kg−1 · min−1, CVR increased 77 ± 51% in preterm fetuses and 41 ± 11% in near-term fetuses, and at 75 μg · kg−1 · min−1, CVR increased 80 ± 33% in preterm fetuses and 83 ± 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under α-adrenergic blockade (phenoxybenzamine, n = 5) and under dopaminergic D1-receptor blockade (SCH-23390, n = 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D1-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, α-adrenergic response to an increase in blood pressure.
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Morrison, J. L., K. J. Botting, J. L. Dyer, S. J. Williams, K. L. Thornburg, and I. C. McMillen. "Restriction of placental function alters heart development in the sheep fetus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, no. 1 (July 2007): R306—R313. http://dx.doi.org/10.1152/ajpregu.00798.2006.
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Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110–125 days of gestation (term: 150 ± 3 days). PR fetuses with a mean gestational Po2 < 17 mmHg were defined as hypoxic. At postmortem (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.
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Wagner, Kenneth R., Pauline Ting, Margaret V. Westfall, Shun-Ichi Yamaguchi, John D. Bacher, and Ronald E. Myers. "Brain Metabolic Correlates of Hypoxic-Ischemic Cerebral Necrosis in Mid-Gestational Sheep Fetuses: Significance of Hypotension." Journal of Cerebral Blood Flow & Metabolism 6, no. 4 (August 1986): 425–34. http://dx.doi.org/10.1038/jcbfm.1986.75.
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Midgestational sheep fetuses exposed to marked hypoxia for 2 h remain brain intact if MABP is maintained above 30 mm Hg. On the other hand, similarly hypoxic fetuses, if they experience reductions in MABP below 30 mm Hg, develop foci of necrosis that predominantly affect hemispheric white matter and neostriatum. Cortex damage is more restricted and is usually associated with more massive underlying white matter damage. The present study examines the brain metabolic basis for the important role of hypotension in brain injury development in marked hypoxia. Sheep fetuses rendered hypoxic by respiring their ewes with 11% oxygen (fetal Pao2 = 8–12 mm Hg) in which MABP was maintained above 30 mm Hg showed increases in brain lactic acid concentrations to 7–13 μmol/g but unaltered energy charge. In contrast, fetuses that sustained MABP reductions below 30 mm Hg showed increases in lactic acid concentrations in vulnerable structures to 16–24 μmol/g accompanied by marked decreases in energy charge. The vulnerable structures also showed reductions in fructose concentrations but a variable behavior of other brain metabolites including phosphocreatine, glycogen, and glucose. Thus, the present findings suggest a relation between hypotension during marked hypoxia, low energy charge, lactic acid accumulation in brain at high concentrations, and fetal brain injury. The ewes of hypoxic hypotensive fetuses received pentobarbital at lower doses than did those of fetuses that maintained blood pressure. This suggests that pentobarbital plays an important role in protecting the fetal brain from asphyxia by extending the hypoxic fetus's ability to maintain blood pressure in addition to reducing its brain metabolism.
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Helou, S., R. C. Koehler, C. A. Gleason, M. D. Jones, and R. J. Traystman. "Cerebrovascular autoregulation during fetal development in sheep." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 3 (March 1, 1994): H1069—H1074. http://dx.doi.org/10.1152/ajpheart.1994.266.3.h1069.
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There are scant data regarding the development of cerebrovascular autoregulation in fetuses. We tested the hypothesis that a decrease in cerebrovascular resistance (CVR) at reduced cerebral perfusion pressure (CPP) is absent in midgestation and near-term fetal sheep. Catheters were chronically implanted for microsphere determination of cerebral blood flow (CBF) in 9 fetuses at 92 days and in 10 fetuses at 132 days gestation (full term = 145 days). CPP was reduced by ventricular infusion of artificial cerebrospinal fluid. In 92-day fetuses, CPP was reduced stepwise from 35 to 25 and 18 mmHg and CBF decreased from 52 +/- 5 to 43 +/- 4 and 27 +/- 5 (SE) ml.min-1 x 100 g-1, respectively. Half of the immature fetuses showed some reduction in CVR at moderate reduction in CPP; however, there was no significant change in CVR in the group as a whole (from 0.72 +/- 0.06 to 0.61 +/- 0.04 and 0.89 +/- 0.20 mmHg.ml-1.min.100 g). In 132-day fetuses, CPP was reduced from 45 to 33 and 28 mmHg and CBF was unchanged (from 105 +/- 7 to 97 +/- 11 and 89 +/- 8 ml.min-1 x 100 g-1). CVR decreased from 0.45 +/- 0.05 to 0.41 +/- 0.08 and 0.33 +/- 0.03 mmHg.ml-1.min.100 g. There were no significant changes in arterial blood gases at reduced CPP in either age group. We conclude that cerebrovascular autoregulation at reduced CPP is not well developed at 92 days (0.63 gestation) in fetal sheep but that autoregulatory capacity is evident near term. We speculate that poor autoregulation may place the premature fetal brain at risk for injury.
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Macko, Antoni R., Dustin T. Yates, Xiaochuan Chen, Leslie A. Shelton, Amy C. Kelly, Melissa A. Davis, Leticia E. Camacho, Miranda J. Anderson, and Sean W. Limesand. "Adrenal Demedullation and Oxygen Supplementation Independently Increase Glucose-Stimulated Insulin Concentrations in Fetal Sheep With Intrauterine Growth Restriction." Endocrinology 157, no. 5 (March 3, 2016): 2104–15. http://dx.doi.org/10.1210/en.2015-1850.
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Abstract In pregnancies complicated by placental insufficiency and intrauterine growth restriction (IUGR), fetal glucose and oxygen concentrations are reduced, whereas plasma norepinephrine and epinephrine concentrations are elevated throughout the final third of gestation. Here we study the effects of chronic hypoxemia and hypercatecholaminemia on β-cell function in fetal sheep with placental insufficiency-induced IUGR that is produced by maternal hyperthermia. IUGR and control fetuses underwent a sham (intact) or bilateral adrenal demedullation (AD) surgical procedure at 0.65 gestation. As expected, AD-IUGR fetuses had lower norepinephrine concentrations than intact-IUGR fetuses despite being hypoxemic and hypoglycemic. Placental insufficiency reduced fetal weights, but the severity of IUGR was less with AD. Although basal plasma insulin concentrations were lower in intact-IUGR and AD-IUGR fetuses compared with intact-controls, glucose-stimulated insulin concentrations were greater in AD-IUGR fetuses compared with intact-IUGR fetuses. Interestingly, AD-controls had lower glucose- and arginine-stimulated insulin concentrations than intact-controls, but AD-IUGR and AD-control insulin responses were not different. To investigate chronic hypoxemia in the IUGR fetus, arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction. Oxygenation of IUGR fetuses enhanced glucose-stimulated insulin concentrations 3.3-fold in intact-IUGR and 1.7-fold in AD-IUGR fetuses but did not lower norepinephrine and epinephrine concentrations. Together these findings show that chronic hypoxemia and hypercatecholaminemia have distinct but complementary roles in the suppression of β-cell responsiveness in IUGR fetuses.
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Gitler, M. S., M. M. Piccio, J. E. Robillard, and P. A. Jose. "Characterization of renal alpha-adrenoceptor subtypes in sheep during development." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, no. 2 (February 1, 1991): R407—R412. http://dx.doi.org/10.1152/ajpregu.1991.260.2.r407.
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Intrarenal arterial infusion of alpha 1-adrenergic agonists decreases renal blood flow, glomerular filtration rate, and water and sodium excretion to a greater extent in fetus and newborn than in adult sheep. In vitro renal vascular effects of alpha 1- and alpha 2-adrenergic agonists are also greater in fetus than newborn or adult. The present studies were designed to examine the ontogeny of renal alpha-adrenoceptor subtypes in sheep for whom the renal effects of alpha-adrenergic agonists have been described at similar postconceptional ages. With the use of radioligand-binding techniques, specific binding of [3H]prazosin (alpha 1-adrenergic antagonist), [3H]idazoxan, and [3H]rauwolscine (alpha 2-adrenergic antagonists) was studied in fetus, lamb, and adult sheep kidneys. The specific binding of the three radioligands was greatest in fetal and least in adult kidneys. Analysis of Scatchard plots revealed a greater renal alpha 1-adrenoceptor density in fetuses than in lamb or adults. Renal alpha 2-adrenoceptor density was also greater in fetuses than in lambs. These studies suggest that the increased renal alpha 1- and alpha 2-adrenergic effects in fetal sheep are related to increased alpha-adrenoceptor density. Competition experiments and rank adrenergic antagonist potency suggested the presence of only the alpha 1b-adrenoceptor in fetal and adult sheep kidneys. The alpha 2-adrenoceptor that was found only in the fetal sheep had a low affinity to rauwolscine, which is unlike that described in most species for alpha 2-adrenoceptors.
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Orgeig, Sandra, Tamara A. Crittenden, Ceilidh Marchant, I. Caroline McMillen, and Janna L. Morrison. "Intrauterine growth restriction delays surfactant protein maturation in the sheep fetus." American Journal of Physiology-Lung Cellular and Molecular Physiology 298, no. 4 (April 2010): L575—L583. http://dx.doi.org/10.1152/ajplung.00226.2009.
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Pulmonary surfactant is synthesized by type II alveolar epithelial cells to regulate the surface tension at the air-liquid interface of the air-breathing lung. Developmental maturation of the surfactant system is controlled by many factors including oxygen, glucose, catecholamines, and cortisol. The intrauterine growth-restricted (IUGR) fetus is hypoxemic and hypoglycemic, with elevated plasma catecholamine and cortisol concentrations. The impact of IUGR on surfactant maturation is unclear. Here we investigate the expression of surfactant protein (SP) A, B, and C in lung tissue of fetal sheep at 133 and 141 days of gestation (term 150 ± 3 days) from control and carunclectomized Merino ewes. Placentally restricted (PR) fetuses had a body weight <2 SD from the mean of control fetuses and a mean gestational PaO2<17 mmHg. PR fetuses had reduced absolute, but not relative, lung weight, decreased plasma glucose concentration, and increased plasma cortisol concentration. Lung SP-A, -B, and -C protein and mRNA expression was reduced in PR compared with control fetuses at both ages. SP-B and -C but not SP-A mRNA expression and SP-A but not SP-B or -C protein expression increased with gestational age. Mean gestational PaO2was positively correlated with SP-A, -B, and -C protein and SP-B and -C mRNA expression in the younger cohort. SP-A and -B gene expression was inversely related to plasma cortisol concentration. Placental restriction, leading to chronic hypoxemia and hypercortisolemia in the carunclectomy model, results in significant inhibition of surfactant maturation. These data suggest that IUGR fetuses are at significant risk of lung complications, especially if born prematurely.
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Longo, L. D., A. D. Hull, D. M. Long, and W. J. Pearce. "Cerebrovascular adaptations to high-altitude hypoxemia in fetal and adult sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 264, no. 1 (January 1, 1993): R65—R72. http://dx.doi.org/10.1152/ajpregu.1993.264.1.r65.
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In the fetus and infant, high-altitude hypoxemia is associated with increased cerebrovascular morbidity. To test the hypothesis that this increased morbidity involves changes in cerebrovascular endothelial and smooth muscle function, we examined middle cerebral, posterior communicating, basilar, and common carotid arteries obtained from 23 normoxic fetuses, 19 hypoxemic fetuses maintained at high altitude (3,820 m) from 30 days gestation to near term (approximately 143 days), 55 normoxic non-pregnant adults, and 24 hypoxemic nonpregnant adults maintained at the same altitude and duration as the hypoxemic fetuses. Long-term hypoxemia was associated with several significant changes in both fetal and adult arteries, including a generalized increase in base-soluble protein (5-50%), a depression of the maximum potassium-induced tensions (16-49%), and a depression of the relaxation responses to S-nitroso-N-acetylpenicillamine (1-11%), which releases nitric oxide into solution upon hydration. Altitude acclimatization significantly enhanced amine-to-potassium ratios (the ratio of tension produced by 10 microM serotonin with 20 microM histamine to that produced by 122 mM potassium) only in adult cerebral arteries (51-87%) and significantly depressed potassium-induced stresses (up to 41%) and serotonin/histamine-induced tensions (20-37%) only in fetuses. Endothelium-dependent relaxations to A23187 were significantly depressed in hypoxemic fetuses (4-11%) but were significantly enhanced in hypoxemic adults (2-14%). We conclude that chronic hypoxemia depresses both vascular smooth muscle and endothelial function to a greater extent in fetal than in adult cerebral arteries and that this effect could contribute to the greater postnatal vulnerability to asphyxic and hypertensive insults seen in hypoxemic neonates.
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Leite, Ana Greice Borba, Weliton Galdino da Silva, Daniela Oliveira, and Márcia Bersane Araújo de Medeiros Torres. "Toracoxifopagia em ovinos neonatos – relato de caso." Revista Agraria Academica 3, no. 6 (November 1, 2020): 117–21. http://dx.doi.org/10.32406/v3n62020/117-121/agrariacad.
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Thoracoxypophagia consists of the union of two fetuses by the chest and xiphoid region, it is a rare congenital alteration. This study aimed to report a case of thoracoxypophagia in sheep. A sheep with dystocic delivery was attended, who had the first fetus of normal birth, but lifeless, requiring a cesarean section for the second birth. After the surgery, a congenital malformation of the thoracoxypophagia type was found between two fetuses, who were stillborn. Similar reports have not been found in the literature, as it is a rare condition, which may be related to several factors, such as viruses, drugs, teratogenic plants and inbreeding, leading to gestation to a dysthocic delivery and incompatibility with life.
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Thorn, Stephanie R., Satya M. Sekar, Jinny R. Lavezzi, Meghan C. O'Meara, Laura D. Brown, William W. Hay, and Paul J. Rozance. "A physiological increase in insulin suppresses gluconeogenic gene activation in fetal sheep with sustained hypoglycemia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 303, no. 8 (October 15, 2012): R861—R869. http://dx.doi.org/10.1152/ajpregu.00331.2012.
Full textAbstract:
Reduced maternal glucose supply to the fetus and resulting fetal hypoglycemia and hypoinsulinemia activate fetal glucose production as a means to maintain cellular glucose uptake. However, this early activation of fetal glucose production may be accompanied by hepatic insulin resistance. We tested the capacity of a physiological increase in insulin to suppress fetal hepatic gluconeogenic gene activation following sustained hypoglycemia to determine whether hepatic insulin sensitivity is maintained. Control fetuses (CON), hypoglycemic fetuses induced by maternal insulin infusion for 8 wk (HG), and 8 wk HG fetuses that received an isoglycemic insulin infusion for the final 7 days (HG+INS) were studied. Glucose and insulin concentrations were 60% lower in HG compared with CON fetuses. Insulin was 50% higher in HG+INS compared with CON and four-fold higher compared with HG fetuses. Expression of the hepatic gluconeogenic genes, PCK1, G6PC, FBP1, GLUT2, and PGC1A was increased in the HG and reduced in the HG+INS liver. Expression of the insulin-regulated glycolytic and lipogenic genes, PFKL and FAS, was increased in the HG+INS liver. Total FOXO1 protein expression, a gluconeogenic activator, was 60% higher in the HG liver. Despite low glucose, insulin, and IGF1 concentrations, phosphorylation of AKT and ERK was higher in the HG liver. Thus, a physiological increase in fetal insulin is sufficient for suppression of gluconeogenic genes and activation of glycolytic and lipogenic genes in the HG fetal liver. These results demonstrate that fetuses exposed to sustained hypoglycemia have maintained hepatic insulin action in contrast to fetuses exposed to placental insufficiency.
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Forhead, A. J., L. Thomas, J. Crabtree, N. Hoggard, D. S. Gardner, D. A. Giussani, and A. L. Fowden. "Plasma Leptin Concentration in Fetal Sheep during Late Gestation: Ontogeny and Effect of Glucocorticoids." Endocrinology 143, no. 4 (April 1, 2002): 1166–73. http://dx.doi.org/10.1210/endo.143.4.8762.
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Abstract The ontogeny and developmental control of plasma leptin concentration in the fetus are poorly understood. The present study investigated plasma leptin concentration in chronically catheterized sheep fetuses near term, and in neonatal and adult sheep. The effect of glucocorticoids on plasma leptin in utero was examined by fetal adrenalectomy and exogenous cortisol or dexamethasone infusion. In intact, untreated fetuses studied between 130 and 140 d (term, 145 ± 2 d), plasma leptin concentration increased in association with the prepartum cortisol surge. Positive relationships were observed between plasma leptin in utero and both gestational age and plasma cortisol. Plasma leptin was also inversely correlated with fetal paO2. The ontogenic rise in plasma leptin was abolished by fetal adrenalectomy. In intact fetuses at 123–127 d, plasma leptin was increased by infusions of cortisol (3–5 mg kg−1d−1, +127 ± 21%) for 5 d and dexamethasone (45–60 μg kg−1d−1, +268 ± 61%) for 2 d. However, the cortisol-induced rise in plasma leptin was transient; by the fifth day of infusion, plasma leptin was restored to within the baseline range. These findings show that, in the sheep fetus, an intact adrenal gland is required for the normal ontogenic rise in plasma leptin near term. Furthermore, fetal treatment with exogenous and endogenous glucocorticoids increases circulating leptin concentration in utero.
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Kawashima, I., ED Zanjani, G. Almaida-Porada, AW Flake, H. Zeng, and M. Ogawa. "CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells." Blood 87, no. 10 (May 15, 1996): 4136–42. http://dx.doi.org/10.1182/blood.v87.10.4136.bloodjournal87104136.
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Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.
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Fowden, AL, J. Mapstone, and AJ Forhead. "Regulation of glucogenesis by thyroid hormones in fetal sheep during late gestation." Journal of Endocrinology 170, no. 2 (August 1, 2001): 461–69. http://dx.doi.org/10.1677/joe.0.1700461.
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The effects of thyroid hormone deficiency in utero on the fetal glucogenic capacity were investigated by measuring glucose production and hepatic levels of glycogen and gluconeogenic enzymes in normal sheep fetuses in the fed and fasted states during late gestation and in those made thyroid hormone deficient by fetal thyroidectomy (TX). In the fed state, fetal TX had no effect on glucose uptake, utilisation or production by the fetus. It also had no apparent effect on the glycogen content or activities of the key gluconeogenic enzymes in the fetal liver. In addition, fetal plasma concentrations of insulin, cortisol, adrenaline or noradrenaline were unaffected by fetal TX in the fed state. In contrast, the rates of fetal O(2) consumption and CO(2) production per kilogram fetal bodyweight were significantly lower in TX than in intact fetuses in the fed state (P<0.05). TX prevented fetal glucose production in response to maternal fasting for 48 h. It also abolished the normal decreases in the fetal glucose carbon oxidation fraction, the rate of CO(2) production from glucose carbon and in the fraction of the umbilical O(2) uptake used for glucose carbon oxidation that occur during fasting in intact fetuses. At the end of the fast, plasma noradrenaline concentrations and hepatic levels of glycogen, glucose 6-phosphatase, fructose diphosphatase and alanine aminotransferase were significantly lower in TX than in intact fetuses. These observations show that thyroid hormones are essential for glucogenesis in the sheep fetus during late gestation and suggest that these hormones act both on the hepatic glucogenic pathways and on the mechanisms activating glucogenesis in utero.
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Jeffray, Treena M., Edward T. M. Berdusco, John R. G. Challis, Megan Wallace, and Abigail Fowden. "Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep." Canadian Journal of Physiology and Pharmacology 73, no. 11 (November 1, 1995): 1568–73. http://dx.doi.org/10.1139/y95-216.
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The effects of incremental cortisol infusion or fetal adrenalectomy on plasma corticosteroid-binding capacity (CBC) were examined in sheep fetuses during late gestation (term ≈ 150 days). Cortisol, infused from day 120 at 1.5 mg/day for the first 3 days, 2.5 mg/day for the next 5 days, and 3.5 mg/day for the final 2 days, stimulated a significant rise in plasma CBC and immunoreactive corticosteroid binding globulin (CBG). There was a significant positive correlation between individual values for total plasma cortisol concentrations and CBC values. In contrast, fetal adrenalectomy at day 115 prevented the rise in plasma CBC found in intact fetuses at term. These experiments show that exogenous cortisol, given in a manner that mimics the prepartum rise in fetal plasma cortisol, stimulates CBG biosynthesis, whereas abolition of the cortisol rise prevents the increase in CBG. The study provides strong support for the proposal that the prepartum increase in CBG biosynthesis in fetal sheep occurs in response to the progressive rise in adrenal cortisol output by the fetus towards term.Key words: corticosteroid binding globulin, cortisol, adrenalectomy, fetus, sheep.
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Wassink, Guido, Laura Bennet, Lindsea C. Booth, Ellen C. Jensen, Bert Wibbens, Justin M. Dean, and Alistair Jan Gunn. "The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep." Journal of Applied Physiology 103, no. 4 (October 2007): 1311–17. http://dx.doi.org/10.1152/japplphysiol.00396.2007.
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There is evidence that preterm fetuses have blunted chemoreflex-mediated responses to hypoxia. However, the preterm fetus has much lower aerobic requirements than at term, and so moderate hypoxia may not be sufficient to elicit maximal chemoreflex responses; there are only limited quantitative data on the ontogeny of chemoreflex and hemodynamic responses to severe asphyxia. Chronically instrumented fetal sheep at 0.6 ( n = 12), 0.7 ( n = 12), and 0.85 ( n = 8) of gestational age (GA; term = 147 days) were exposed to 30, 25, or 15 min of complete umbilical cord occlusion, respectively. At all ages, occlusion was associated with early onset of bradycardia, profoundly reduced femoral blood flow and conductance, and hypertension. The 0.6-GA fetuses showed a significantly slower and lesser fall in femoral blood flow and conductance compared with the 0.85-GA group, with a correspondingly reduced relative rise in mean arterial blood pressure. As occlusion continued, the initial adaptation was followed by loss of peripheral vasoconstriction and progressive development of hypotension in all groups. The 0.85-GA fetuses showed significantly more sustained reduction in femoral conductance but also more rapid onset of hypotension than either of the younger groups. Electroencephalographic (EEG) activity was suppressed during occlusion in all groups, but the degree of suppression was less at 0.6 GA than at term. In conclusion, the near-midgestation fetus shows attenuated initial (chemoreflex) peripheral vasomotor responses to severe asphyxia compared with more mature fetuses but more sustained hemodynamic adaptation and reduced suppression of EEG activity during continued occlusion of the umbilical cord.
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Hasan, S. U., and A. Rigaux. "Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep." Journal of Applied Physiology 73, no. 4 (October 1, 1992): 1402–12. http://dx.doi.org/10.1152/jappl.1992.73.4.1402.
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To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves.
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Wu, S. Y., D. H. Polk, W. S. Huang, A. Reviczky, K. Wang, and D. A. Fisher. "Sulfate conjugates of iodothyronines in developing sheep: effect of fetal hypothyroidism." American Journal of Physiology-Endocrinology and Metabolism 265, no. 1 (July 1, 1993): E115—E120. http://dx.doi.org/10.1152/ajpendo.1993.265.1.e115.
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We recently showed that thyroxine sulfate (T4S) and 3,3',5-triiodothyronine sulfate (T3S) were major thyroid hormone metabolites in ovine fetuses and neonates. To further characterize the sulfation pathway in ovine fetuses, we measured 3,3',5'-triiodothyronine (rT3S) in serum and other body fluids in samples obtained from fetal (n = 23, 94-145 days of gestational age, term = 150 days), newborn (n = 6), and adult (n = 6) sheep. In addition, T3S, T4S, and rT3S levels were measured in tissue fluids and serum samples obtained from ovine fetuses 13 days after total thyroidectomy (Tx) conducted at gestational age of 110-113 days (n = 5). Sham-operated twin fetuses served as controls (n = 5). The relative order of mean rT3S concentration for various tissue fluids in fetuses were meconium > bile > serum > allantoic fluid > urine or amniotic fluid. Peak mean tissue fluid levels generally occurred at 110-130 days gestation. In hypothyroid fetuses, significant decreases in the mean serum concentrations of T4S and rT3S, but not T3S, were noted. The mean rT3S level also was decreased significantly in allantoic fluid, bile, and meconium, whereas T4S and T3S levels were reduced only in bile of the Tx fetuses. These data demonstrate that sulfation is a major pathway in thyroid hormone metabolism in both euthyroid and hypothyroid ovine fetuses.
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Galinsky, Robert, Timothy J. M. Moss, Lina Gubhaju, Stuart B. Hooper, M. Jane Black, and Graeme R. Polglase. "Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep." American Journal of Physiology-Renal Physiology 301, no. 2 (August 2011): F280—F285. http://dx.doi.org/10.1152/ajprenal.00066.2011.
Full textAbstract:
Chorioamnionitis is an antecedent of preterm birth. We aimed to determine the effect of experimental chorioamnionitis in fetal sheep during late gestation on 1) nephron number, 2) renal corpuscle volume, and 3) renal inflammation. We hypothesized that exposure to chorioamnionitis would lead to inflammation in fetal kidneys and adversely impact on the development of nephrons, leading to a reduction in nephron number. At ∼121 days of gestation (term ∼147 days), pregnant ewes bearing twin or singleton fetuses received a single intra-amniotic injection of lipopolysaccharide ( n = 6; 3 singletons, 3 twins); controls were either untreated or received an intra-amniotic injection of saline ( n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At ∼128 days of gestation, fetuses were delivered via Caesarean section. Kidneys were collected and stereologically analyzed to determine nephron number and renal corpuscle volume. Renal inflammation was assessed using immunohistochemistry. Experimental chorioamnionitis did not affect body weight or relative kidney weight. There was a significant reduction in nephron number but no change in renal corpuscle volume in LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18% in singleton and twin LPS-exposed fetuses, respectively. The degree of renal inflammation did not differ between groups. Importantly, this study demonstrates that exposure to experimental chorioamnionitis adversely impacts on nephron number in the developing fetus.
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Rigatto, H., M. Moore, and D. Cates. "Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep." Journal of Applied Physiology 61, no. 1 (July 1, 1986): 160–64. http://dx.doi.org/10.1152/jappl.1986.61.1.160.
Full textAbstract:
The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.
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Fowden, A. L., and A. J. Forhead. "Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term." American Journal of Physiology-Endocrinology and Metabolism 300, no. 1 (January 2011): E94—E102. http://dx.doi.org/10.1152/ajpendo.00205.2010.
Full textAbstract:
In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose ultilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.
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Anderson, D. F., A. Barbera, and J. J. Faber. "Substantial reductions in blood pressure after bilateral nephrectomy in fetal sheep." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 1 (January 1, 1994): H17—H20. http://dx.doi.org/10.1152/ajpheart.1994.266.1.h17.
Full textAbstract:
The role of the kidneys in the maintenance of arterial blood pressure was examined in fetal sheep. Surgery was performed on 11 pregnant sheep (8 twin pregnancies) at approximately 125 days. All 19 fetuses were instrumented with hindlimb arterial and venous catheters. Eleven of the fetuses (but only 1 of each twin) were also bilaterally nephrectomized. Fetal arterial blood pressure was measured several times between 2 and 14 days after surgery. Arterial blood pressure in the intact fetuses increased from 44 +/- 1 to 47 +/- 1 mmHg (SE) but gradually decreased from 37 +/- 4 to 25 +/- 3 mmHg in the nephrectomized group. Whereas the arterial blood pressures measured on the first day of the experiment were not statistically significantly different between the two groups, by the final day of the experiment the arterial blood pressure of the intact fetuses was much higher than that of the nephrectomized fetuses. Venous blood pressure was similar in the two groups. We conclude that bilateral nephrectomy in fetal sheep not only stops the normal gestational increase in arterial blood pressure but also leads to a progressive decline.
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Davis, Melissa A., Leticia E. Camacho, Alexander L. Pendleton, Andrew T. Antolic, Rosa I. Luna-Ramirez, Amy C. Kelly, Nathan R. Steffens, Miranda J. Anderson, and Sean W. Limesand. "Augmented glucose production is not contingent on high catecholamines in fetal sheep with IUGR." Journal of Endocrinology 249, no. 3 (June 1, 2021): 195–207. http://dx.doi.org/10.1530/joe-21-0071.
Full textAbstract:
Fetuses with intrauterine growth restriction (IUGR) have high concentrations of catecholamines, which lowers the insulin secretion and glucose uptake. Here, we studied the effect of hypercatecholaminemia on glucose metabolism in sheep fetuses with placental insufficiency-induced IUGR. Norepinephrine concentrations are elevated throughout late gestation in IUGR fetuses but not in IUGR fetuses with a bilateral adrenal demedullation (IAD) at 0.65 of gestation. Euglycemic (EC) and hyperinsulinemic–euglycemic (HEC) clamps were performed in control, intact-IUGR, and IAD fetuses at 0.87 of gestation. Compared to controls, basal oxygen, glucose, and insulin concentrations were lower in IUGR groups. Norepinephrine concentrations were five-fold higher in IUGR fetuses than in IAD fetuses. During the EC, rates of glucose entry (GER, umbilical + exogenous), glucose utilization (GUR), and glucose oxidation (GOR) were greater in IUGR groups than in controls. In IUGR and IAD fetuses with euglycemia and euinsulinemia, glucose production rates (GPR) remained elevated. During the HEC, GER and GOR were not different among groups. In IUGR and IAD fetuses, GURs were 40% greater than in controls, which paralleled the sustained GPR despite hyperinsulinemia. Glucose-stimulated insulin concentrations were augmented in IAD fetuses compared to IUGR fetuses. Fetal weights were not different between IUGR groups but were less than controls. Regardless of norepinephrine concentrations, IUGR fetuses not only develop greater peripheral insulin sensitivity for glucose utilization but also develop hepatic insulin resistance because GPR was maintained and unaffected by euglycemia or hyperinsulinemia. These findings show that adaptation in glucose metabolism of IUGR fetuses are independent of catecholamines, which implicate that hypoxemia and hypoglycemia cause the metabolic responses.
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Boulanger, L., P. Chavatte-Palmer, D. Lebouhris, N. Daniel, Y. Heyman, L. Gall, N. Borenstein, and C. Cotinot. "325 GENERATION OF A CLONED GREEN FLUORESCENT PROTEIN (GFP) EXPRESSING TRANSGENIC SHEEP FOR MUSCLE STEM CELL GRAFT EXPERIMENTS." Reproduction, Fertility and Development 23, no. 1 (2011): 259. http://dx.doi.org/10.1071/rdv23n1ab325.
Full textAbstract:
Sheep are a good model for cardiopathy and surgery training in medical studies because organ volumes are similar to humans. Grafting of stem cells collected from skeletal muscles is a major area of research into treatments for heart failure. To establish an efficient protocol it is first necessary to follow the fate of grafted cells in an animal model. The aim of the project was to obtain 2 cloned sheep of the same genetic background, 1 conventional and 1 expressing green fluorescent protein (GFP), to be used for graft experiments. First, chimeric transgenic fetuses were generated by transduction of 8-cell stage embryos with a lentivirus expressing GFP under the EF1a human ubiquitous promoter. A large dilution of the lentivirus solution was used so that only some cells were transduced. Chimeric transgenic embryos were examined for GFP expression and transferred to recipients at the blastocyst stage. At 50 days of pregnancy, 8 fetuses were obtained. Three showed stable but mosaic expression of GFP in some tissues, as expected. The proportion of green cells ranged from 20 to 80% between fetuses. To make sure that low-level expression was not overlooked in GFP-negative fetuses, skin cells from each of the 8 fetuses were cultured for 10 days to isolate green from white cell colonies. This step confirmed the negative signal in 5 fetuses, but also led to the elimination of 1 positive fetus whose cells tended to switch off the GFP signal. Only 1 fetus yielded a good enough ratio of white to green cell colonies to enable the freezing of cells, which were subsequently used in 4 NT experiments. In total, 42 blastocysts were transferred to 20 recipients, of which 4 reached late pregnancy. A GFP-positive cloned fetus was delivered by C-section 4 days before term and required no intensive care. This animal is now over 6 months old and clinically normal. Expression of GFP in skin is stable and readily visualised with specialised GFP glasses. Global expression of GFP in all tissues will be followed in an F1 generation to avoid risk of contamination after biopsies in this first precious animal. Weekly ultrasound examination revealed the onset of fetal suffering (abdominal fluid accumulation, reduced heart rate, and fetal movements) in the last week before term in 3 other fetuses. These did not survive despite emergency C-section and intensive neonatal care. Fetal anomalies were similar to those observed in bovine NT. Gross placental abnormalities, however, were not present. None of the postmortem observations could be attributed to lentivirus integration as they were similar to those seen in nontransgenic cloned animals. Experiments are now proceeding to generate a normal white cloned sheep by NT using frozen nontransgenic cells from the same fetus. This will allow generation of sheep with the same genetic background that can be used to develop muscle stem cell grafting protocols. The authors thank M. Bonneau, CRII, for help in C-section, and J. P. Albert, J. Massoneau, and S. Rotg for animal care.
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Young, Sharla F., Stephen B. Tatter, Nancy K. Valego, Jorge P. Figueroa, Jalonda Thompson, and James C. Rose. "The role of hypothalamic input on corticotroph maturation in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 284, no. 6 (June 1, 2003): R1621—R1630. http://dx.doi.org/10.1152/ajpregu.00572.2002.
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Corticotropin-releasing hormone receptor type 1 (CRH-R1) expression 1 and vasopressin type 1b (V1b) receptor protein decrease in late-gestation fetal sheep. Because hypothalamo-pituitary disconnection (HPD) has been demonstrated to prevent the morphological maturation of corticotrophs, we hypothesized that hypothalamic input is necessary for the maturational changes in CRH-R1 and V1b receptor levels. We measured CRH-R1 and V1b receptor expression in the anterior pituitaries of fetuses at 140 days gestational age (dGA) that underwent HPD or sham surgery at 120 dGA. CRH-R1 mRNA decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. However, CRH-R1 protein levels were elevated in HPD fetuses compared with sham and were not different from 120 dGA values. V1b protein levels decreased similarly in HPD and sham-operated fetuses compared with 120 dGA naive fetuses. We conclude that hypothalamic input to the pituitary is necessary for the decrease in CRH-R1 receptor protein levels in late-gestation fetal sheep. However, hypothalamic input is not necessary for the decrease in V1b receptor expression seen in late gestation.
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Benjamin, Joshua S., Christine B. Culpepper, Laura D. Brown, Stephanie R. Wesolowski, Sonnet S. Jonker, Melissa A. Davis, Sean W. Limesand, Randall B. Wilkening, William W. Hay, and Paul J. Rozance. "Chronic anemic hypoxemia attenuates glucose-stimulated insulin secretion in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 312, no. 4 (April 1, 2017): R492—R500. http://dx.doi.org/10.1152/ajpregu.00484.2016.
Full textAbstract:
Fetal insulin secretion is inhibited by acute hypoxemia. The relationship between prolonged hypoxemia and insulin secretion, however, is less well defined. To test the hypothesis that prolonged fetal hypoxemia impairs insulin secretion, studies were performed in sheep fetuses that were bled to anemic conditions for 9 ± 0 days (anemic, n = 19) and compared with control fetuses ( n = 15). Arterial hematocrit and oxygen content were 34% and 52% lower, respectively, in anemic vs. control fetuses ( P < 0.0001). Plasma glucose concentrations were 21% higher in the anemic group ( P < 0.05). Plasma norepinephrine and cortisol concentrations increased 70% in the anemic group ( P < 0.05). Glucose-, arginine-, and leucine-stimulated insulin secretion all were lower ( P < 0.05) in anemic fetuses. No differences in pancreatic islet size or β-cell mass were found. In vitro, isolated islets from anemic fetuses secreted insulin in response to glucose and leucine as well as control fetal islets. These findings indicate a functional islet defect in anemic fetuses, which likely involves direct effects of low oxygen and/or increased norepinephrine on insulin release. In pregnancies complicated by chronic fetal hypoxemia, increasing fetal oxygen concentrations may improve insulin secretion.
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Chen, Xiaochuan, Alice S. Green, Antoni R. Macko, Dustin T. Yates, Amy C. Kelly, and Sean W. Limesand. "Enhanced insulin secretion responsiveness and islet adrenergic desensitization after chronic norepinephrine suppression is discontinued in fetal sheep." American Journal of Physiology-Endocrinology and Metabolism 306, no. 1 (January 1, 2014): E58—E64. http://dx.doi.org/10.1152/ajpendo.00517.2013.
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Intrauterine growth-restricted (IUGR) fetuses experience prolonged hypoxemia, hypoglycemia, and elevated norepinephrine (NE) concentrations, resulting in hypoinsulinemia and β-cell dysfunction. Previously, we showed that acute adrenergic blockade revealed enhanced insulin secretion responsiveness in the IUGR fetus. To determine whether chronic exposure to NE alone enhances β-cell responsiveness afterward, we continuously infused NE into fetal sheep for 7 days and, after terminating the infusion, evaluated glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-induced insulin secretion (GPAIS). During treatment, NE-infused fetuses had greater ( P < 0.05) plasma NE concentrations and exhibited hyperglycemia ( P < 0.01) and hypoinsulinemia ( P < 0.01) compared with controls. GSIS during the NE infusion was also reduced ( P < 0.05) compared with pretreatment values. GSIS and GPAIS were approximately fourfold greater ( P < 0.01) in NE fetuses 3 h after the 7 days that NE infusion was discontinued compared with age-matched controls or pretreatment GSIS and GPAIS values of NE fetuses. In isolated pancreatic islets from NE fetuses, mRNA concentrations of adrenergic receptor isoforms (α1D, α2A, α2C, and β1), G protein subunit-αi-2, and uncoupling protein 2 were lower ( P < 0.05) compared with controls, but β-cell regulatory genes were not different. Our findings indicate that chronic exposure to elevated NE persistently suppresses insulin secretion. After removal, NE fetuses demonstrated a compensatory enhancement in insulin secretion that was associated with adrenergic desensitization and greater stimulus-secretion coupling in pancreatic islets.
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Stonestreet, Barbara S., Katherine H. Petersson, Grazyna B. Sadowska, and Clifford S. Patlak. "Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults." Journal of Applied Physiology 96, no. 2 (February 2004): 553–60. http://dx.doi.org/10.1152/japplphysiol.00617.2003.
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We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation ( r = 0.72, n = 24, P = 0.0001), premature lambs ( r = 0.58, n = 22, P = 0.005), newborn lambs ( r = 0.57, n = 24, P = 0.004), and adult sheep ( r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep.
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Reller, M. D., M. J. Morton, G. D. Giraud, D. E. Wu, and K. L. Thornburg. "Maximal myocardial blood flow is enhanced by chronic hypoxemia in late gestation fetal sheep." American Journal of Physiology-Heart and Circulatory Physiology 263, no. 4 (October 1, 1992): H1327—H1329. http://dx.doi.org/10.1152/ajpheart.1992.263.4.h1327.
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The measurement of maximal myocardial blood flow gives information about the total cross-sectional area of the coronary resistance vessels. During a continuous left atrial infusion of adenosine (60 micrograms.kg-1.min-1), maximal myocardial blood flow was measured in 4 fetuses hypoxemic for a minimum of 5-8 days (pH = 7.33 +/- 0.01, arterial PCO2 = 49.8 +/- 4.2 Torr, arterial PO2 = 16.1 +/- 1.3 Torr, and arterial concentration of O2 = 5.3 +/- 1.2 ml/dl). These data were compared with an identically instrumented group of normoxemic fetuses (n = 7) following the same study protocol (pH = 7.38 +/- 0.02, arterial PCO2 = 43.1 +/- 3.8 Torr, arterial PO2 = 19.8 +/- 2.0 Torr, and arterial concentration of O2 = 7.9 +/- 1.0 ml/dl) (P < 0.05). At comparable arterial pressures, the maximal myocardial flow (ml.min-1.100 g tissue-1) for hypoxemic vs. normoxemic fetuses was 974 +/- 273 and 630 +/- 181 for the total myocardium, 986 +/- 367 and 602 +/- 192 for the left ventricular free wall, 1,025 +/- 346 and 614 +/- 178 for the septum, and 1,231 +/- 274 and 757 +/- 269 for the right ventricular free wall, respectively (P < 0.01). These data suggest that hypoxemia in the fetus can significantly alter the coronary vascular bed, which, if confirmed, would represent an important adaptation in the developing fetus.
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Stonestreet, Barbara S., Joyce M. Oen-Hsiao, Katherine H. Petersson, Grazyna B. Sadowska, and Clifford S. Patlak. "Regulation of brain water during acute hyperosmolality in ovine fetuses, lambs, and adults." Journal of Applied Physiology 94, no. 4 (April 1, 2003): 1491–500. http://dx.doi.org/10.1152/japplphysiol.00923.2002.
Full textAbstract:
In adult rats, when plasma osmolality increases, water flows across the blood-brain barrier down its concentration gradient from brain to plasma, and brain volume deceases. The brain responds to this stress by gaining osmotically active solutes, which limit water loss. This phenomenon is termed brain volume (water) regulation. We tested the hypothesis that brain volume regulation is more effective in young lambs and adult sheep than in fetuses, premature lambs, and newborn lambs. Brain water responses to acute hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60 and 90% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, young lambs at 20–30 days of age, and adult sheep. After exposure of the sheep to increases in systemic osmolality with mannitol plus NaCl, brain water content and electrolytes were quantified. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. There were significant differences from an ideal osmometer in the cerebral cortex of fetuses at 90% of gestation, cerebral cortex, and cerebellum of newborn lambs, and cerebral cortex, cerebellum, and medulla of young lambs and adult sheep; however, there were no differences in the brain regions of fetuses at 60% of gestation and premature lambs, cerebellum and medulla of fetuses at 90% of gestation, and medulla of newborn lambs. We conclude that 1) brain water loss is maximal and brain volume regulation impaired in most brain regions of fetuses at 60 and 90% of gestation and premature lambs; 2) brain volume regulation develops first in the cerebral cortex of the fetuses at 90% of gestation and in the cerebral cortex and cerebellum of newborn lambs, and then it develops in the medulla of the lambs at 20–30 days of age; 3) brain water loss is limited and volume regulation present in the brain regions of young lambs and adult sheep; and 4) the ability of the brain to exhibit volume regulation develops in a region- and age-related fashion.
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Brace, R. A. "Thoracic duct lymph flow and its measurement in chronically catheterized sheep fetus." American Journal of Physiology-Heart and Circulatory Physiology 256, no. 1 (January 1, 1989): H16—H20. http://dx.doi.org/10.1152/ajpheart.1989.256.1.h16.
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A method was developed for chronic catheterization of the left thoracic lymph duct at the base of the neck in the sheep fetus, which did not disrupt the other major lymphatic vessels that join the venous circulation at the same location. The lymphatic catheter was connected to a catheter in a jugular vein when lymph flow was not being recorded, so that the lymph continuously returned to the fetal circulation. Special consideration of catheter size to minimize flow resistance and treatment to prevent clotting were required. Individual animals were maintained up to 17 days with lymph flow continuing. In 13 fetuses averaging 128 days gestation (term = 147 days) at the time of catheterization, lymph flow rate was measured for 1 h each day for the first 7 postsurgical days with an on-line computer technique that continuously calculated lymph flow rate. Lymph flow averaged 0.64 +/- 0.17 (SD) ml/min in fetuses weighing 2.3-4 kg and tended to undergo a nonsignificant increase with time. Lymph and plasma protein concentrations did not change with time. In individual fetuses, large spontaneous variations in lymph flow rate occurred over periods of several seconds to a few minutes. Analysis showed that these variations in flow rate were not associated with fetal breathing movements. Thus the present study describes a technique for studying the dynamics of lymph flow in the unanesthetized sheep fetus in utero over a time period limited primarily by the length of gestation. In addition, it appears that thoracic duct lymph flow rate in the fetus per unit body weight averages three to four times that in the adult.
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Levitsky, L. L., J. B. Paton, and D. E. Fisher. "Precursors to glycogen in ovine fetuses." American Journal of Physiology-Endocrinology and Metabolism 255, no. 5 (November 1, 1988): E743—E747. http://dx.doi.org/10.1152/ajpendo.1988.255.5.e743.
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Postprandial hepatic glycogenesis in the adult animal is now felt to proceed largely through gluconeogenic pathways rather than directly from glucose. The ovine fetus, like the mature sheep, lacks specific hepatic glucokinase. Therefore, we examined the role of lactate as a fetal glycogenic precursor in seven chronically catheterized 125-day sheep fetuses. Fetuses were infused with L-[U-14C]lactate and D-[3-3H]glucose (50 microCi load, 50 microCi/h for 5 h), while maternal glucose was maintained at 50 mg/dl. Mean fetal hepatic glycogen specific activity (microCi/mg x 10(3] was 0.82 +/- 0.08 for 14C and 2.6 +/- 0.4 for 3H, whereas fetal renal glycogen specific activity was 0.46 +/- 0.22 for 14C and 0.78 +/- 0.16 for 3H. In contrast, [14C]glucose specific activity was undetectable in blood (limit of detectability 1 microCi/mg x 10(3] and mean [3H]glucose specific activity was 8.9 +/- 1.3 microCi/mg x 10(3]. The least detectable specific activity of [14C]glucose did not differ significantly from the [14C]glycogen enrichment in liver, whereas [3H]glucose specific activity was significantly (P less than 0.02) greater than [3H]glycogen enrichment. We conclude that glycogenesis from glucose is partly through the indirect gluconeogenic route and that lactate may be a glycogenic precursor in the ovine fetus.
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Wagerle, L. C., C. D. Kurth, and R. A. Roth. "Sympathetic reactivity of cerebral arteries in developing fetal lamb and adult sheep." American Journal of Physiology-Heart and Circulatory Physiology 258, no. 5 (May 1, 1990): H1432—H1438. http://dx.doi.org/10.1152/ajpheart.1990.258.5.h1432.
Full textAbstract:
The response of cerebral arteries to norepinephrine was examined in vivo in six dated preterm fetal (94-121 days gestation), eight term fetal (127-141 days gestation), five newborn (7-14 days), and five adult sheep, anesthetized and equipped with a closed cranial window. Norepinephrine (10(-8)-10(-4) M in cerebrospinal fluid) caused a dose-dependent decrease in pial arteriolar diameter in fetal and newborn lambs; however, preterm fetuses were 7- and 14-fold more sensitive to norepinephrine than term fetuses and newborn lambs, respectively. The effective concentration of norepinephrine inducing a 15% decrease in diameter (EC15) was 4.6 +/- 1.8, 33 +/- 11, and 64 +/- 23 microM, for the respective ages. Adult cerebral arterioles did not contract to norepinephrine. In preterm and term fetuses, the contractile response to norepinephrine was blocked by alpha 1-antagonist, prazosin (3 mg iv), and was enhanced by cocaine (10(-5) M; EC15 = 0.086 +/- 0.04 and 1.84 +/- 1.20 microM, respectively) indicating that alpha 1-adrenoceptors mediate the response and that the decrease in sensitivity is not caused by development of neuronal uptake processes. In seven fetuses (111-141 days; mean 123 days gestation), electrical stimulation of the superior cervical sympathetic ganglion constricted pial arterioles by 21 +/- 5%; this contractile response was also blocked by prazosin. The cerebral arterioles of the fetus in utero possess a functional sympathetic innervation capable of influencing cerebrovascular resistance. There is a loss of responsiveness of cerebral arterioles to norepinephrine during fetal and postnatal development, suggesting that the contribution of neuroadrenergic mechanisms to cerebrovascular regulation may be relatively unique to the immature brain.