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1

Chen, Dahu, Padmaja Ganapathy, Li-Ji Zhu, Xueping Xu, Quanxi Li, Indrani C. Bagchi та Milan K. Bagchi. "Potential Regulation of Membrane Trafficking by Estrogen Receptorα via Induction of Rab11 in Uterine Glands during Implantation". Molecular Endocrinology 13, № 6 (1 червня 1999): 993–1004. http://dx.doi.org/10.1210/mend.13.6.0287.

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Анотація:
Abstract The steroid hormone estrogen profoundly influences the early events in the uterus leading to embryo implantation. It is thought that estrogen triggers the expression of a unique set of genes in the preimplantation endometrium that in turn control implantation. To identify these estrogen-induced genes, we used a delayed implantation model system in which embryo attachment to endometrium is dependent on estrogen administration. Using a mRNA differential display (DD) method, we isolated a number of cDNAs representing mRNAs whose expression is either turned on or turned off in response to an implantation-inducing dose of estrogen. We identified one of these cDNAs as that encoding rab11, a p21ras-like GTP-binding protein (G protein), which functions in the targeting of transport vesicles to the plasma membrane. In normal pregnant rats, rab11 mRNA was expressed at low levels on days 1–2 of pregnancy, but its expression was markedly enhanced (∼6- to 8-fold) between days 3–5 immediately before implantation. In situ hybridization and immunocytochemistry revealed that rab11 expression in the uterus was predominantly in the glandular epithelium. In ovariectomized rats, the expression of rab11 mRNA was induced in the endometrium in response to estrogen. To determine whether this effect of estrogen was mediated through its nuclear receptors, we examined rab11 expression in a transformed endometrial cell line, Ishikawa. In transient transfection experiments, we observed that overexpression of estrogen receptor (ER) α or β induced endogenous rab11 mRNA in a hormone-dependent manner. ER bound to an antagonist, ICI 182,780, failed to activate this gene expression. These findings, together with the observation that ERα but not ERβ is detected in the glands of the preimplantation uterus, indicate that rab11 is one of the proteins that are specifically induced by estrogen-complexed ERα in rat endometrium at the onset of implantation. Our results imply that estrogen, which induces the synthesis of many growth factors and their receptors and other secretory proteins that are thought to be critical for implantation, may also facilitate their transport to the membrane and/or secretion by stimulating the expression of rab11, a component of the membrane-trafficking pathway. This study therefore provides novel insights into the diverse cellular mechanisms by which estrogen, acting via its nuclear receptors, may influence blastocyst implantation.
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2

Cao, Li-Hua, Jing-Yi Qiao, Hui-Yuan Huang, Xiao-Yan Fang, Rui Zhang, Ming-San Miao, and Xiu-Min Li. "PI3K–AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model." Molecules 24, no. 20 (October 15, 2019): 3700. http://dx.doi.org/10.3390/molecules24203700.

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Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K–AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E2), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K–AKT pathway-related proteins.
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3

Temple-Smith, P., and T. Grant. "Platypus Venom and Envenomation." Australian Mammalogy 20, no. 2 (1998): 314. http://dx.doi.org/10.1071/am98330.

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Анотація:
Curiosity and controversy have surrounded the function of the crural system of the platypus since its discovery in the late 18th century. Early work on the venom confused rather than clarified the biological significance of the crural system. Many experiments gave conflicting results, especially concerning the coagulation effects of intravenous injections of venom extracts, although consistent observations were made of general vasodilation following intravenous injection into rabbits. More recent studies have shown that crural (venom) gland activity is seasonal and in synchrony with the breeding season. Secretion from the crural glands shows proteolytic activity and contains at least three major proteins, one of which has hyaluronidase activity. Subcutaneous injection of venom produced mild toxic effects whereas intravenous doses (75-90mg protein/kg) in mice were lethal. Whole venom induced local oedema after subplantar injection in rats and a 4.2kD peptide isolated from the venom caused relaxation of rat uterus in vitro. At least 16 incidents of envenomation by the platypus have been recorded in humans but no fatalities have been reported. In most human cases, envenomation resulted in immediate and severe local pain and oedema, sometimes associated with nausea, cold sweats, dull gastric pain and vomiting, hyperaesthesia and swelling of the axillary lymph nodes. Significant functional impairment of the upper limb for some weeks or months has been observed. Various treatments have been used to alleviate the symptoms of envenomation with differing successes. Envenomation has also been recorded in platypuses and dogs. The effects of these envenomations will be discussed.
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4

Wira, C. R., J. E. Bodwell, and R. H. Prabhala. "In vivo response of secretory component in the rat uterus to antigen, IFN-gamma, and estradiol." Journal of Immunology 146, no. 6 (March 15, 1991): 1893–99. http://dx.doi.org/10.4049/jimmunol.146.6.1893.

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Abstract Intrauterine immunization of ovariectomized rats with SRBC is known to elicit pronounced IgA and IgG antibody responses in uterine secretions of immunized uteri. To determine whether secretory component (SC), the receptor for transporting polymeric IgA from tissues to mucosal surfaces, was also influenced by Ag, ovariectomized rats were immunized and boosted by placing SRBC into the lumena of individual uterine horns. In response to Ag, the levels of polymeric IgA, as well as free SC and SC bound to polymeric IgA, increased in uterine secretions. When ovariectomized animals were treated with estradiol, a fivefold increase in SC levels was observed in the immunized horns, indicating that a hormone response is superimposed on the Ag-induced stimulation of uterine SC. To determine whether IFN-gamma influences the presence of SC in uterine secretions, IFN-gamma was placed in the uterine lumena of ovariectomized nonimmunized rats. When uterine secretions were analyzed, significantly higher levels of SC were found in IFN-gamma-exposed uteri than were present in saline treated control animals. In contrast, intrauterine instillation of IFN-gamma had no effect on the levels of IgA in uterine secretions. This response was specific for IFN-gamma in that IFN-alpha/beta had no effect on uterine SC or IgA levels. These results indicate that intrauterine instillation of Ag, in addition to evoking pronounced antibody responses, stimulates the production of SC, which may be responsible for the transport of polymeric IgA from tissue to uterine secretions. Furthermore, they indicate that IFN-gamma placed in the uterine lumen stimulates SC production and suggest that the uterine SC response to Ag may be mediated by the action of IFN-gamma on uterine epithelial cells.
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5

Wira, C. R., and C. P. Sandoe. "Specific IgA and IgG antibodies in the secretions of the female reproductive tract: effects of immunization and estradiol on expression of this response in vivo." Journal of Immunology 138, no. 12 (June 15, 1987): 4159–64. http://dx.doi.org/10.4049/jimmunol.138.12.4159.

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Abstract Uterine and vaginal secretions collected from intact adult female rats were analyzed to determine whether immunization at sites distal to the reproductive tract had any effect on the presence of specific IgA and IgG antibodies in genital tract secretions. Peyer's patch and i.p. immunization and boost with sheep red blood cells (SRBC) stimulated the appearance of specific IgA antibodies in uterine and vaginal secretions of uterine-ligated animals. IgG antibodies were also induced in uterine but not in vaginal secretions. In contrast, subcutaneous immunization and boost elicited a weak IgA uterine and IgG vaginal response. To establish the role of estradiol in regulating the presence of specific antibodies in the female genital tract, ovariectomized rats received primary and/or secondary Peyer's patch immunizations with hormone treatment. Administration of estradiol daily for 3 days before sacrifice resulted in a significant accumulation of IgA and IgG antibodies to SRBC in uterine secretions. In the absence of estradiol, antibody content was negligible. Vaginal antibody levels were also clearly influenced by estradiol. In contrast to the uterus, however, specific IgA and IgG antibodies were present in the vaginal secretions of saline-injected immunized animals and were markedly inhibited in animals treated with estradiol. These results indicate that antibodies in genital tract secretions can be induced by immunization of the Peyer's patches and that their presence in uterine secretions is clearly dependent on estradiol. Further, they indicate that gut-derived specific antibodies enter the vagina in the absence of hormone stimulation and that estradiol exerts an inhibitory effect on their presence in vaginal secretions.
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6

Aurich, C., T. Beyer, and D. Scarlet. "51 Effects of modulating early luteal phase progestin concentration on endometrial function in early pregnant mares." Reproduction, Fertility and Development 31, no. 1 (2019): 151. http://dx.doi.org/10.1071/rdv31n1ab51.

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Анотація:
Progesterone prepares the endometrium for pregnancy. This requires down-regulation of progesterone receptors in the endometrial epithelium as a prerequisite for the expression of pregnancy-associated proteins. We investigated effects of modulated peripheral progestin concentration in early luteal phase mares on endometrial function on Day 14 of pregnancy. Genitally healthy oestrous mares (n=8; age 4 to 14 years) were inseminated until ovulation and treated with either altrenogest (0.044mg kg−1 once daily orally) on Days 5 to 10 after ovulation (ALT), cloprostenol (125mg once daily intramuscularly) on Days 0 to 3 after ovulation (CLO) or left untreated (CON). The ALT and CLO treatments were chosen to increase and decrease total peripheral progestin concentration, respectively. Each treatment was given to every mare in consecutive cycles at random order. On Day 14 after ovulation, endometrial fluid was collected with a cotton roll (Salivette, Sarstedt, Germany) inserted into the uterus and an endometrial biopsy for immunohistological examination was collected. In endometrial fluid, free amino acid concentrations were analysed by ion exchange liquid chromatography with an amino acid analyser (Institut Kuhlmann, Analytik-Zentrum Ludwigshafen, Germany). Cell nuclei staining positive for the progesterone receptor were determined in the luminar and glandular epithelium as well as in the stroma. Statistical analysis was performed by non-parametric Friedman test with subsequent Wilcoxon test. Values are given as mean±standard error of mean. Pregnancy rate was 0.6±0.1 (13 cycles/8 pregnancies), 1.0±0 (8 cycles/8 pregnancies), and 0.7±0.1 (11 cycles/8 pregnancies) in CON, ALT, and CLO cycles, respectively (P=0.062). Conceptus size between Days 10 and 14 did not differ among treatments. The percentage of luminal epithelial cells staining positive for progesterone receptor differed among treatments (CON 72.8±4.1, ALT 70.7±4.7, and CLO 84.1±1.9%; P<0.05) and was higher in CLO than in ALT and CON cycles (P<0.05). Free amino acids glutamic acid and glycine were most abundant in endometrial fluid, but their concentrations did not differ among treatments. The concentrations of the amino acids isoleucine (CON 0.17±0.03, CLO 0.14±0.02, and ALT 0.23±0.04 µmol) and lysine (CON 0.27±0.08, CLO 0.18±0.05, and ALT 0.44±0.13 µmol) were influenced by treatment (P<0.05) and lower in CLO than in ALT and CON cycles. In conclusion, impaired luteal function due to CLO treatment during the early luteal phase of pregnant mares delayed down-regulation of progesterone receptors in the endometrial epithelium on Day 14. This influenced endometrial function as reflected in lower concentrations of the amino acids lysine and isoleucine in endometrial secretions.
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7

Leslie, M. V., P. J. Hansen, and G. R. Newton. "Uterine secretions of the cow contain proteins that are immunochemically related to the major progesterone-induced proteins of the sheep uterus." Domestic Animal Endocrinology 7, no. 4 (October 1990): 517–26. http://dx.doi.org/10.1016/0739-7240(90)90009-o.

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8

Kumar, Archana, T. B. Sridharn, and Kamini A. Rao. "Role of Seminal Plasma Proteins in Effective Zygote Formation- A Success Road to Pregnancy." Protein & Peptide Letters 26, no. 4 (March 28, 2019): 238–50. http://dx.doi.org/10.2174/0929866526666190208112152.

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Анотація:
Seminal plasma proteins contributed by secretions of accessory glands plays a copious role in fertilization. Their role is overlooked for decades and even now, as Artificial Reproduction Techniques (ART) excludes the plasma components in the procedures. Recent evidences suggest the importance of these proteins starting from imparting fertility status to men, fertilization and till successful implantation of the conceptus in the female uterus. Seminal plasma is rich in diverse proteins, but a major part of the seminal plasma is constituted by very lesser number of proteins. This makes isolation and further research on non abundant protein a tough task. With the advent of much advanced proteomic techniques and bio informatics tools, studying the protein component of seminal plasma has become easy and promising. This review is focused on the role of seminal plasma proteins on various walks of fertilization process and thus, the possible exploitation of seminal plasma proteins for understanding the etiology of male related infertility issues. In addition, a compilation of seminal plasma proteins and their functions has been done.
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9

Bunsueb, Sudtida, Nareelak Tangsrisakda, Alexander T. H. Wu, and Sitthichai Iamsaard. "Localization (and profiles) of tyrosinephosphorylated proteins in female reproductive organs of adult rats." Clinical and Experimental Reproductive Medicine 47, no. 3 (September 1, 2020): 180–85. http://dx.doi.org/10.5653/cerm.2020.03573.

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Objective: Tyrosine phosphorylation is an essential process in many biological systems, including the male reproductive system. The presence of tyrosine-phosphorylated (TyrPho) proteins has been well documented in male reproductive organs, but research in fertile females is still limited.Methods: The ovary, oviduct, and uterus of adult female Sprague-Dawley rats in the estrus phase were used to localize TyrPho proteins using an immunohistochemical technique. These proteins were separated and their expression patterns were examined by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and Western blot analysis, respectively.Results: TyrPho proteins were localized in the cytoplasm of the oocyte except the antral fluid; in the granulosa cells, theca cells, and stromal cells of the ovary; at the apical surface of oviductal epithelial cells; and in the basal epithelium and submucosa of the uterine wall. Moreover, we found that 72-, 43-, and 28-kDa TyrPho proteins were localized in the ovary, while 170-, 55-, and 43-kDa proteins were localized in the oviduct. In the uterus, we detected four major bands, corresponding to 61-, 55-, 54-, and 43-kDa TyrPho proteins.Conclusion: Given that these TyrPho proteins were found in major reproductive organs in the estrus phase, these proteins may play important roles in female fertility.
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10

Lindeberg, Heli, Richard J. S. Burchmore, and Malcolm W. Kennedy. "Pulse of inflammatory proteins in the pregnant uterus of European polecats ( Mustela putorius ) leading to the time of implantation." Royal Society Open Science 4, no. 3 (March 2017): 161085. http://dx.doi.org/10.1098/rsos.161085.

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Анотація:
Uterine secretory proteins protect the uterus and conceptuses against infection, facilitate implantation, control cellular damage resulting from implantation, and supply pre-implantation embryos with nutrients. Unlike in humans, the early conceptus of the European polecat ( Mustela putorius ; ferret) grows and develops free in the uterus until implanting at about 12 days after mating. We found that the proteins appearing in polecat uteri changed dramatically with time leading to implantation. Several of these proteins have also been found in pregnant uteri of other eutherian mammals. However, we found a combination of two increasingly abundant proteins that have not been recorded before in pre-placentation uteri. First, the broad-spectrum proteinase inhibitor α 2 -macroglobulin rose to dominate the protein profile by the time of implantation. Its functions may be to limit damage caused by the release of proteinases during implantation or infection, and to control other processes around sites of implantation. Second, lipocalin-1 (also known as tear lipocalin) also increased substantially in concentration. This protein has not previously been recorded as a uterine secretion in pregnancy in any species. If polecat lipocalin-1 has similar biological properties to that of humans, then it may have a combined function in antimicrobial protection and transporting or scavenging lipids. The changes in the uterine secretory protein repertoire of European polecats is therefore unusual, and may be representative of pre-placentation supportive uterine secretions in mustelids (otters, weasels, badgers, mink, wolverines) in general.
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11

Molnar, P., and L. J. Murphy. "Effects of oestrogen on rat uterine expression of insulin-like growth factor-binding proteins." Journal of Molecular Endocrinology 13, no. 1 (August 1994): 59–67. http://dx.doi.org/10.1677/jme.0.0130059.

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ABSTRACT Previous studies have established that the IGFs are involved in oestrogen-induced uterine proliferation. IGF-binding proteins (IGFBPs) are present in most biological fluids and tissues and may modulate the actions of the IGFs. We examined uterine, hepatic and renal expression of the IGFBPs throughout the oestrous cycle and investigated the effects of oestradiol (OE2) on IGFBP expression in ovariectomized (ovx) rats. Uterine expression of IGFBPs-1 and -3 showed a definite variation throughout the oestrous cycle with highest levels during dioestrus. In the liver and kidney the changes in IGFBP-1 and IGFBP-3 mRNA abundance were the opposite of those observed in the uterus, with the highest levels observed during oestrus. Administration of OE2 to ovx rats decreased uterine IGFBP-3 mRNA and increased IGFBP-4 mRNA levels. In these rats there were no consistent changes in renal IGFBP-1 or IGFBP-3 mRNAs; however, a significant increase in IGFBP-4 mRNA was observed in this tissue, as in the uterus. In the liver an increase in IGFBP-1 mRNA and a decrease in IGFBP-3 mRNA levels were observed in rats treated with OE2. Despite changes in uterine, hepatic and renal IGFBP mRNA levels, no significant variation was seen in serum IGFBPs as determined by ligand blotting of sera. These data demonstrate that there is a cyclical variation in the expression of the IGFBPs in the uterus, kidney and liver, and that OE2 is able to modulate differentially IGFBP expression in these tissues.
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12

O’Neil, Eleanore V., Gregory W. Burns, Christina R. Ferreira, and Thomas E. Spencer. "Characterization and regulation of extracellular vesicles in the lumen of the ovine uterus†." Biology of Reproduction 102, no. 5 (February 14, 2020): 1020–32. http://dx.doi.org/10.1093/biolre/ioaa019.

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Abstract Secretions of the endometrium are vital for peri-implantation growth and development of the sheep conceptus. Extracellular vesicles (EVs) are present in the uterine lumen, emanate from both the endometrial epithelia of the uterus and trophectoderm of the conceptus, and hypothesized to mediate communication between those cell types during pregnancy establishment in sheep. Size-exclusion chromatography and nanoparticle tracking analysis determined that total EV number in the uterine lumen increased from days 10 to 14 of the cycle but was lower on days 12 and 14 of pregnancy in sheep. Intrauterine infusions of interferon tau (IFNT) did not affect total EV number in the uterine lumen. Quantitative mass spectrometric analyses defined proteins and lipids in EVs isolated from the uterine lumen of day 14 cyclic and pregnant sheep. In vitro analyses found that EVs decreased ovine trophectoderm cell proliferation and increased IFNT production without effects on gene expression as determined by RNA-seq. Collective results support the idea EVs impact conceptus growth during pregnancy establishment via effects on trophectoderm cell growth.
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13

Esponda, Pedro. "Gene transfer to the mammalian reproductive tract." Zygote 19, no. 4 (December 13, 2010): 287–95. http://dx.doi.org/10.1017/s0967199410000523.

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SummaryThis review summarizes the results of research on gene transfer to the mammalian genital tract. Gene transfer experiments have been developed during the last 2 decades and have been applied using in vitro, ex vivo and in vivo procedures. (i) In vitro methods have been applied to the uterine epithelial cells with the principal purpose of analysing some pathological change occurring in the uterus. In the male tract, epididymal cell lines have been used to evaluate the expression of particular genes and the function of specific proteins. (ii) Ex vivo methods have been applied to both the uterus and the vas deferens in humans, and good transgene expression has been recorded. (iii) In vivo gene transfer in the female tract has been employed in the uterus and oviduct using gene injections or electroporation methods. The glandular epithelium of both organs can be transfected efficiently, and transfection efficiency depends on the hormonal stage of the animal. The best expression occurred during pseudopregnancy and meta-estrus periods, when high progesterone and low estradiol concentrations occur. In the male tract, in vivo methods have been applied to mouse vas deferens and epididymis. In both organs, patches of epithelial regions appeared to express the transgenes. Furthermore, the secretions of both organs were also modified using gene constructions that led to the expression of some secretory proteins. In summary, gene modifications in the epithelium of the mammalian reproductive tract have been successful employing different technologies. Further improvements in transfection efficiency would help provide new insights into the physiology of these reproductive organs. Furthermore, the use of these methods could also be used to modify the fertility of mammals.
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14

Mir, Amaidah, Hammad Ahmed Butt, Maria Yasmeen, Anber Saleem, Ruqqia Shafi Minhas, and Sumaira Abbasi. "Histomorphological effects of sodium arsenite on uterus of rats." International Journal of Basic & Clinical Pharmacology 9, no. 11 (October 21, 2020): 1641. http://dx.doi.org/10.18203/2319-2003.ijbcp20204454.

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Background: Arsenic is highly toxic agent and a risk factor for disease and disability. Arsenic is present in drinking water of many developing and developed countries including Pakistan and due to rapid industrialization its quantity in soil and water is increasing day by day.Methods: In an 18 month study in which we took two principal groups, labelled as control group A and experimental group B. The animals of experimental group B were administered 4 µg of sodium arsenite dissolved in 10 ml of distilled water by oral gavage daily for 14 days. The uterus was removed and processed for paraffin embedding and stained with hematoxylin and eosin (H and E). The histological parameters; uterine luminal diameter, height of uterine luminal epithelium, area occupied by epithelial component of uterine glands and the thickness of myometrium were measured and evaluated by civil AutoCAD 2013 software. The data was analyzed statistically with the statistical package for social sciences (SPSS).Results: Histological results showed the degenerative effects. The luminal diameter of uterine horns was reduced in experimental animals. The height of uterine epithelium was reduced. Area occupied by epithelial component of uterine glands was reduced along the reduction in the thickness of myometrium.Conclusions: The histological abnormalities observed in uterus showed that the degenerative effects may be due to oxidative stress produced by the exposure to sodium arsenite. As sodium arsenite produces the oxidative stress by the formation of free radicals and by the denaturation of proteins.
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15

Almiñana and Bauersachs. "Extracellular Vesicles in the Oviduct: Progress, Challenges and Implications for the Reproductive Success." Bioengineering 6, no. 2 (April 12, 2019): 32. http://dx.doi.org/10.3390/bioengineering6020032.

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Анотація:
The oviduct is the anatomical part of the female reproductive tract where the early reproductive events take place, from gamete transport, fertilization and early embryo development to the delivery of a competent embryo to the uterus, which can implant and develop to term. The success of all these events rely upon a two-way dialogue between the oviduct (lining epithelium and secretions) and the gametes/embryo(s). Recently, extracellular vesicles (EVs) have been identified as major components of oviductal secretions and pointed to as mediators of the gamete/embryo-maternal interactions. EVs, comprising exosomes and microvesicles, have emerged as important agents of cell-to-cell communication by the transfer of biomolecules (i.e., mRNAs, miRNAs, proteins) that can modulate the activities of recipient cells. Here, we provide the current knowledge of EVs in the oviductal environment, from isolation to characterization, and a description of the EVs molecular content and associated functional aspects in different species. The potential role of oviductal EVs (oEVs) as modulators of gamete/embryo-oviduct interactions and their implications in the success of early reproductive events is addressed. Lastly, we discuss current challenges and future directions towards the potential application of oEVs as therapeutic vectors to improve pregnancy disorders, infertility problems and increase the success of assisted reproductive technologies.
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16

Lu, Dezhang, Wenxiang Hu, Tian Tian, Mengran Wang, Mengru Zhou, and Chenchen Wu. "The Mechanism of Lipopolysaccharide’s Effect on Secretion of Endometrial Mucins in Female Mice during Pregnancy." International Journal of Molecular Sciences 23, no. 17 (September 1, 2022): 9972. http://dx.doi.org/10.3390/ijms23179972.

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Анотація:
The main toxic component of endotoxins released from the death or dissolution of Gram-negative bacteria is lipopolysaccharide (LPS), which exists widely in the natural environment, and a large amount of endotoxin can significantly inhibit the reproductive performance of animals. A previous study showed that endotoxins mainly damaged the physiological function of mucins in the endometrium, but the mechanism is not clear. In this study, the PI3K/Akt signaling pathway was not activated, and the NF-κB signaling pathway was inhibited by LPS treatment; the expression of occludin and E-cadherin proteins were decreased and ZO-1 protein expression was increased, because LPS can lead to the mucous layer becoming thinner, so that the embryonic survival rate is significantly reduced in early pregnancy. In middle and late pregnancy, LPS translocated to the epithelial cells of the uterus and the expression of claudin-1, JAMA, and E-cadherin proteins were decreased; at this time, a large number of glycosaminoglycan particles were secreted by endometrial gland cells through the PI3K/Akt/NF-κB signaling pathway that was activated after LPS treatment, However, there was no significant difference between the survival rates of fetal mice in the LPS (+) and LPS (-) groups. Glycosaminoglycan particles and mucins are secreted by gland cells, which can protect and maintain the pregnancy in the middle and late gestational periods.
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17

An, B. S., and E. B. Jeung. "97 THE REGULATION OF UTERINE CONTRACTION BY ENDOCRINE-DISRUPTING CHEMICALS IN RATS." Reproduction, Fertility and Development 25, no. 1 (2013): 196. http://dx.doi.org/10.1071/rdv25n1ab97.

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Environmental oestrogens, class of endocrine-disrupting chemicals, are defined as compounds that bind the oestrogen receptors and elicit or modulate an ER-mediated response. Examples of suspected environmental oestrogenic chemicals include plastic components such as bisphenol A (BPA) and some components of detergents and their biodegradation products, 4-octylphenol (OP). The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed endometrial waves or contractile waves. The balanced contractile waves play an important role in regulating oestrus or menstrual cycles, implantation, maintaining pregnancy, and parturition. The uterine contraction has been known to be regulated by contraction-associated proteins such as oxytocin, oxytocin receptor (OTR), connexin 43, prostaglandin F2 alpha receptor (FP), and 15-hydroxy prostaglandin dehydrogenase (PDGH). Endogenous steroid hormones including oestrogen and progesterone have been shown to regulate contraction-associated proteins and, thereby, modify uterine contraction. Forty female immature rats were divided into 8 groups, each group composed of 5 rats. They were injected subcutaneously daily for 3 days with BPA and OP at doses of 20, 100, and 500 mg kg–1 of BW per day; 17β-estradiol (E2, 40 µg kg–1 per day) was a positive control. After 24 h of the final treatment, the rats were euthanized and the uteri were collected for further experiments. Total RNA and protein were extracted from uteri. The mRNA expressions for CaBP-9k, oxytocin, OTR, FP, and PDGH were determined by real-time PCR with specific primers, and the protein levels were examined by Western blot assay. The data were analyzed using a one-way ANOVA. The P-values <0.05 were considered statistically significant. The treatment of oestrogenic compounds significantly regulated the contraction-associated proteins. First, the mRNA levels of CaBP-9k that is a biomarker for evaluating oestrogenicity in the rats were significantly induced by positive control, E2. Chemicals OP and BPA at doses of 100 and 500 mg kg–1 also induced the gene expression of CaBP-9k. Oxytocin and OTR were highly augmented by OP (40 fold) and BPA (6-fold) at a dose of 500 mg kg–1 compared with control, whereas PDGH was moderately upregulated by the chemicals. Interestingly, FP was decreased by E2 and high doses of OP and BPA. These results showed that exposure of immature rats to BPA and OP regulated expression of oxytocin, OTR, PDGH, and FP genes in the rat uterus. Taken together, uterine contraction and physiological conformational change of the uterus were affected by exposure to oestrogenic endocrine-disrupting chemicals. Because balanced contractile activity of the uterus maintains regular menstrual cycles, pregnancy, and labor, alteration of the contractility raised by oestrogenic compounds may cause severe adverse effects on the female reproductive system.
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18

Anagnostis, Aristotelis, та Athanasios I. Papadopoulos. "Effects of a diet rich in sesame (Sesamum indicum) pericarp on the expression of oestrogen receptor α and oestrogen receptor β in rat prostate and uterus". British Journal of Nutrition 102, № 5 (14 вересня 2009): 703–8. http://dx.doi.org/10.1017/s0007114509297194.

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The expression of oestrogen receptors (ERα and ERβ) in the prostate and uterus tissues of Wistar rats supplied for 8 weeks with a diet rich in sesame (Sesamum indicum) pericarp (30 %) was monitored. Eight male rats, aged 6 weeks, were divided into a control group fed on a normal diet, and an experimental one, provided with the normal diet enriched with 30 % sesame pericarp. A similar experiment was performed with female rats. At the end of the experiment, the prostate and uterus tissues were surgically removed and kept at − 80°C for up to 2 months. Western blotting and quantitative real-time PCR (qRT-PCR) methods were used in order to investigate the levels of receptor proteins and mRNA. Significant increase in the expression of ERβ in prostate and uterus was evident in both methods, while the magnitude of the observed alteration depended on the applied method. No statistically significant change was observed in the expression of ERα in uterus. In prostate, although the increase was more evident when investigated by means of qRT-PCR, the difference in expression of ERα was not statistically significant. In both tissues, a shift of the ratio of ERα:ERβ in favour of ERβ was evident, indicating, according to existing literature, a beneficial effect of the diet provided upon the health status of the organisms. It is suggested that this effect is attributed to the lignans present in the pericarp which exert phyto-oestrogenic activity.
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19

Bender, David A., Kweku Ghartey-Sam, and Amerjit Singh. "Effects of vitamin B6 deficiency and repletion on the uptake of steroid hormones into uterus slices and isolated liver cells of rats." British Journal of Nutrition 61, no. 3 (May 1989): 619–28. http://dx.doi.org/10.1079/bjn19890149.

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1. In vitro, pyridoxal phosphate extracts steroid-hormone receptors from tight nuclear binding (Cidlowski & Thanassi, 1981); in vitamin B6-deficient rats there is increased and prolonged nuclear accumulation of oestradiol in the uterus and testosterone in the prostate, associated with enhanced biological responsiveness of these target tissues to steroid hormone action (Symes et al. 1984; Bowden et al. 1986).2. Slices of uterus from vitamin B6-deficient rats accumulated more [3H]oestradiol than did tissue from repleted animals. Acute repletion with vitamin B6 (0.5–1 h before killing) further increased the uptake of the steroid.3. Isolated hepatocytes from vitamin B6-deficient rats accumulated more [3H]dexamethasone than did cells from repleted animals. Pre-incubation of the hepatocytes with pyridoxal phosphate resulted in a further increase in the uptake of the steroid.4. The results suggest that in addition to the putative role of pyridoxal phosphate in releasing steroid-hormone-receptor complexes from tight nuclear binding (Cidlowski & Thanassi, 1981), vitamin B6 deficiency may also increase the concentration of steroid-hormone receptors or enzymes and other steroid-binding proteins in target tissues.
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20

Ahn, C., E. J. Hong, and E. B. Jeung. "129 UTERINE EXPRESSION OF TRANSIENT RECEPTOR POTENTIAL MELASTATIN 2 CHANNEL AND ITS REGULATION BY SEX STEROID HORMONES." Reproduction, Fertility and Development 26, no. 1 (2014): 178. http://dx.doi.org/10.1071/rdv26n1ab129.

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The transient potential receptor (TRP) channels are membrane-binding proteins that are non-selectively permeable for cations, such as Ca2+ and Mg2+, in numerous mammalian cells. The extracellular or intracellular ions play key roles in physiological function, including muscle contraction, cytokine production, insulin release, and apoptosis. Although TRPM channels have been implicated in the brain, bone marrow, and spleen, the presence of TRPM2 has been reported in the endometrium of the uterus. To determine whether expression of the TRPM2 gene in the uterus is due to gonadal steroid hormones or a hormone-independent effect, the uterine TRPM2 gene was monitored in mature rats during the oestrous cycle and in immature rats after treatment with gonadal steroid oestrogen (E2), progesterone (P4) with/without their antagonist, ICI 182,780, and RU486. Dramatic induction of the level of TRPM2 mRNA occurs at proestrus, followed by a drop to baseline levels at metestrus, and its level is restored at diestrus. Furthermore, the immune-reactive TRPM2 is observed in stromal cells of the myometrium and endometrium, and changes during the oestrus cycle. In addition, E2-induced TRPM2 is inhibited by co-treatment with P4. Taken together, these results imply that TRPM2 expression levels in the uterus are regulated by gonadal steroid hormones E2 and P4. Results of this study suggest possible involvement of TRPM2 in reproductive function during the oestrous cycle in female rats.
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21

Lindsay, Laura A., and Christopher R. Murphy. "Ovarian hyperstimulation affects fluid transporters in the uterus: a potential mechanism in uterine receptivity." Reproduction, Fertility and Development 26, no. 7 (2014): 982. http://dx.doi.org/10.1071/rd12396.

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Controlled ovarian hyperstimulation is commonly used in fertility treatment. Evidence suggests that this could alter the endometrial environment and influence implantation rate. However, the mechanisms underlying this disruption are unknown. A recently developed rat ovarian hyperstimulation (OH) model found alterations in the localisation and expression of several molecules associated with implantation, as well as an increase in luminal fluid at the time of implantation. The present study investigated the effects of OH in rats on the expression of fluid-transporting molecules aquaporin 5 (AQP5) and claudin 4. The expression of these proteins was investigated in uterine luminal epithelial cells of rats undergoing OH and compared with normal pregnancy. There was a significant increase in AQP5 protein in OH rats at the time of implantation, along with a loss of the mesometrial staining gradient, which is thought to contribute to implantation position. At the same time, there was a significant decrease in claudin 4 protein. These results suggest that OH in rats causes a dysregulation in uterine fluid dynamics through modifications to fluid-transporting molecules, resulting in an unfavourable implantation environment for the blastocyst.
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22

Yang, H., and E. B. Jeung. "259 SODIUM/POTASSIUM/CALCIUM EXCHANGER 3 IS REGULATED BY STEROID HORMONES, ESTROGEN AND PROGESTERONE, IN THE UTERUS OF RAT DURING ESTROUS CYCLE." Reproduction, Fertility and Development 22, no. 1 (2010): 286. http://dx.doi.org/10.1071/rdv22n1ab259.

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As a member of the family of potassium-dependent sodium/calcium exchangers, a sodium/calcium/potassium exchanger, NCKX3, plays a critical role in transport of 1 intracellular calcium and potassium ion in exchange for 4 extracellular sodium ions. Transcripts of NCKX3 were most abundant in the brain and smooth muscle, but in the uterus, aorta, and intestine, this gene expressed at lower levels. Its expression and role in the rat uterus during the estrus cycle have not been elucidated yet. In this study, we further examined the uterine expressions of NCKX3 mRNA and protein in stages during the estrous cycle of mature female Sprague-Dawley (SD) rats and in the absence or presence of sex-steroid hormones estrogen (E2) and progesterone (P4) in immature female SD rats. NCKX3 mRNA was verified by RT-PCR. Western blot analysis was applied to detect NCKX3 with an anti-NCKX3 goat polyclonal antibody. During the rat estrous cycle, uterus expressions of NCKX3 mRNA and proteins were highly expressed 2.5-fold at proestrus compared with those at estrus and diestrus. To examine the role(s) of sex steroids on the regulation of NCKX3 in the uterus of the immature female rat, hormones were prepared in ethanol and the rats were treated with E2 [40 (μg/kg of body weight (BW)], P4 (4 mg/kg of BW), or E2 plus P4 for 3 days. The expression of NCKX3 mRNA and protein increased 2-fold with E2, whereas P4 antagonized E2-stimulated NCKX3 expression, as similarly observed in the uterus. In addition, spatial expression of NCKX3 protein was detected by immunohistochemistry. Uterine NCKX3 protein was abundantly localized in the cytoplasm of the luminal and glandular epithelial cells at proestrus. Taken together, these results indicate that uterine NCKX3 is abundantly expressed in the uterus and controlled by steroid hormones E2 and P4, suggesting that uterine expression of NCKX3 might be involved in reproductive function during the cycle in female rat.
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23

Tasaki, Hirotaka, Lijia Zhao, Keishiro Isayama, Huatao Chen, Nobuhiko Yamauchi, Yasufumi Shigeyoshi, Seiichi Hashimoto та Masa-aki Hattori. "Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells". American Journal of Physiology-Cell Physiology 308, № 7 (1 квітня 2015): C528—C538. http://dx.doi.org/10.1152/ajpcell.00220.2014.

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Uterus circadian rhythms have been implicated in the gestation processes of mammals through entraining of the clock proteins to numerous downstream genes. Bone morphogenetic proteins (BMPs), having clock-controlled regulatory sites in their gene promoters, are expressed in the uterus during decidualization, but the regulation of the Bmp gene expression is poorly understood. The present study was designed to dissect the physiological roles of the uterus oscillators in the Bmp expression using the uterus endometrial stromal cells (UESCs) isolated from Per2-dLuc transgenic rats on day 4.5 of gestation. The in vitro decidualization of UESCs was induced by medroxyprogesterone acetate and 2-O-dibutyryl cAMP. A significant decline of Per2-dLuc bioluminescence activity was induced in decidual cells, and concomitantly, the expression of canonical clock genes was downregulated. Conversely, the expression of the core Bmp genes Bmp2, Bmp4, Bmp6, and Bmp7 was upregulated. In UESCs transfected with Bmal1-specific siRNA, in which Rev-erbα expression was downregulated, Bmp genes, such as Bmp2, Bmp4, and Bmp6 were upregulated. However, Bmp1, Bmp7, and Bmp8a were not significantly affected by Bmal1 silencing. The expression of all Bmp genes was enhanced after treatment with the REV-ERBα antagonist (SR8278), although their rhythmic profiles were differed from each other. The binding of REV-ERBα to the proximal regions of the Bmp2 and Bmp4 promoters was revealed by chromatin immunoprecipitation-PCR analysis. Collectively, these results indicate that the Bmp genes are upregulated by the attenuation of the cellular circadian clock; in particular, its core component REV-ERBα functions as a transcriptional silencer in the Bmp gene family.
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24

Ibrahim, E., T. Sheridan, and S. Mandavilli. "Mesonephric Like-Carcinoma (MLCA) of the Uterus with a Predominant Spindled Morphology: A Case Report." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S76. http://dx.doi.org/10.1093/ajcp/aqab191.160.

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Abstract Introduction/Objective Mesonephric-like carcinoma of the uterus is an increasingly recognized carcinoma with mesonephric differentiation, but without association with mesonephric remnants. We present a case of a 60-year-old woman presented with postmenopausal bleeding. Methods/Case Report Pelvic MRI showed possibly a cervical lobulated lesion (4.4cm) extending into the endocervical canal. Initial biopsy of this mass showed a spindle cell neoplasm raising possibility of an endometrial stromal sarcoma. On subsequent radical hysterectomy, there was a mass arising in the lower uterine segment (LUS) with circumferential cervical involvement. The tumor was comprised of sheets of epithelioid to spindle cells with scant cytoplasm and indistinct cell borders. Abundant mitotic figures and foci of necrosis were identified. Focal areas showed dense sclerosis with cords of cells, and only rare areas showed tubule formation with scant secretions. By immunohistochemistry (IHC), the tumor cells were positive for keratin AE1/AE3 (strong, diffuse), TTF-1, p63, p16, CD10 (with luminal accentuation); PAX8, desmin and caldesmon showed focal/rare positivity. Other markers were negative, including GATA3 (patchy, weak), ER and PR. Mismatch repair proteins were intact. Next-generation sequencing (NGS) revealed a KRAS mutation. Considering strong expression of epithelial markers, focal tubule formation with positive TTF-1 and negative GATA-3 labeling, and absence of identified mesonephric remnants, the tumor was classified as a high-grade mesonephric-like carcinoma of the uterus (LUS). Pelvic lymph nodes were negative (pT2 N0), and the patient is receiving cisplatin and external beam radiation. Results (if a Case Study enter NA) NA Conclusion MLCA with a prominent spindled/sarcomatoid component can be difficult to diagnose. Ancillary testing including a broad IHC panel with TTF-1, GATA-3 and NGS may be useful to aid in the diagnosis.
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25

Artus, Jérôme, Isabelle Hue, and Hervé Acloque. "Preimplantation development in ungulates: a ‘ménage à quatre’ scenario." Reproduction 159, no. 3 (March 2020): R151—R172. http://dx.doi.org/10.1530/rep-19-0348.

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In ungulates, early embryonic development differs dramatically from that of mice and humans and is characterized by an extended period of pre- and peri-implantation development in utero. After hatching from the zona pellucida, the ungulate blastocyst will stay free in the uterus for many days before implanting within the uterine wall. During this protracted peri-implantation period, an intimate dialog between the embryo and the uterus is established through a complex series of paracrine signals. The blastocyst elongates, leading to extreme growth of extra-embryonic tissues, and at the same time, the inner cell mass moves up into the trophoblast and evolves into the embryonic disc, which is directly exposed to molecules present in the uterine fluids. In the peri-implantation period, uterine glands secrete a wide range of molecules, including enzymes, growth factors, adhesion proteins, cytokines, hormones, and nutrients like amino and fatty acids, which are collectively referred to as histotroph. The identification, role, and effects of these secretions on the biology of the conceptus are still being described; however, the studies that have been conducted to date have demonstrated that histotroph is essential for embryonic development and serves a critical function during the pre- and peri implantation periods. Here, we present an overview of current knowledge on the molecular dialogue among embryonic, extraembryonic, and maternal tissues prior to implantation. Taken together, the body of work described here demonstrates the extent to which this dialog enables the coordination of the development of the conceptus with respect to the establishment of embryonic and extra-embryonic tissues as well as in preparation for implantation.
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26

Turner, R. T., L. S. Kidder, M. Zhang, S. A. Harris, K. C. Westerlind, A. Maran, and T. J. Wronski. "Estrogen has rapid tissue-specific effects on rat bone." Journal of Applied Physiology 86, no. 6 (June 1, 1999): 1950–58. http://dx.doi.org/10.1152/jappl.1999.86.6.1950.

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The decrease in cancellous bone formation after estrogen treatment is generally thought to be coupled with a prior decrease in bone resorption. To test the possibility that estrogen has rapid tissue-specific actions on bone metabolism, we determined the time course (1–32 h) effects of diethylstilbestrol on steady-state mRNA levels for immediate-response genes, extracellular matrix proteins, and signaling peptides in the proximal tibial metaphysis and uterus by using Northern blot and RNase protection assays. The regulation of signaling peptides by estrogen, although tissue specific, followed a similar time course in bone and uterus. The observed rapid decreases in expression of insulin-like growth factor I, a growth factor associated with bone formation; decreases in mRNA levels for bone matrix proteins; evidence for reduced bone matrix synthesis; failure to detect rapid increases in mRNA levels for signaling peptides implicated in mediating the inhibitory effects of estrogen on bone resorption (interleukin-1 and -6) as well as other cytokines that can increase bone resorption; and the comparatively long duration of the bone remodeling cycle in rats indicate that estrogen can decrease bone formation by a mechanism that does not require a prior reduction in bone resorption.
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27

Mohd Mokhtar, Helmy, Nelli Giribabu, Normadiah Kassim, Sekaran Muniandy, and Naguib Salleh. "Testosterone decreases fluid and chloride secretions in the uterus of adult female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR) expression and functional activity." Journal of Steroid Biochemistry and Molecular Biology 144 (October 2014): 361–72. http://dx.doi.org/10.1016/j.jsbmb.2014.08.007.

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28

Durrer, Stefan, Kirsten Maerkel, Margret Schlumpf, and Walter Lichtensteiger. "Estrogen Target Gene Regulation and Coactivator Expression in Rat Uterus after Developmental Exposure to the Ultraviolet Filter 4-Methylbenzylidene Camphor." Endocrinology 146, no. 5 (May 1, 2005): 2130–39. http://dx.doi.org/10.1210/en.2004-1272.

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Abstract Because the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of nonclassical ER agonists. UV filters from cosmetics represent new classes of endocrine active chemicals, including the preferential ERβ ligands 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor. We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, and 47 mg/kg·d) administered in feed to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. 4-MBC altered steady-state levels of mRNAs encoding for ERα, ERβ, progesterone receptor (PR), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-wk-old offspring. Western-blot analyses of the same tissue homogenates indicated changes in ERα and PR but not ERβ proteins. To assess sensitivity to estradiol (E2), offspring were ovariectomized on d 70, injected with E2 (10 or 50 μg/kg sc) on d 84, and killed 6 h later. Acute up-regulation of PR and IGF-I and down-regulation of ERα and androgen receptor by E2 were dose-dependently reduced in 4-MBC-exposed rats. The reduced response to E2 was accompanied by reduced coactivator SRC-1 mRNA and protein levels. Our data indicate that developmental exposure to 4-MBC affects the regulation of estrogen target genes and the expression of nuclear receptor coregulators in uterus at mRNA and protein levels.
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29

Yang, H., and E. B. Jeung. "99 THE DIFFERENTIAL EXPRESSION OF CALCIUM-RELATED PROTEINS BY HYPOXIC STRESS IN THE DUODENUM, KIDNEY, AND PLACENTA OF PREGNANT RATS." Reproduction, Fertility and Development 25, no. 1 (2013): 197. http://dx.doi.org/10.1071/rdv25n1ab99.

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Preeclampsia is a pregnancy-specific disease characterized by the de novo development of concurrent hypertension, proteinuria, and oxidative stress in placenta. Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Oxidative stress, resulting from deficient remodeling of spiral arteries, is an important inducer of preeclampsia. The potassium-dependent sodium/calcium exchangers including NCKX3 and NCX1 play critical roles in the transport of intracellular calcium that is exchanged with extracellular sodium ions. Calcium-related proteins, NCXs, calbindin, calcium pumping proteins (TRPV5-6, PMCA1b), transcripts are abundant in the smooth muscle, uterus, aorta, and intestine. The expressions of calcium-related proteins in the kidney, duodenum, and placenta after hypoxic stress in rats at gestation Day 19.5 (GD 19.5) were examined by real-time PCR and Western blot analysis. Hypoxic condition did not change fetal weight; however, it significantly increased the weight of placenta compared to normoxic condition. In GD 19.5, renal NCKX3 and TRPV6 expressions were increased, whereas the levels of NCX1 were decreased in hypoxic rats compared with normoxic pregnant rats. The expressions of CaBP-9k, TRPV5, and PMCA1b were not altered in normoxic or hypoxic rat tissues. Duodenal expressions of CaBP-9k, TRPV5-6, and PMCA1 were decreased in hypoxic rats, whereas NCXs were not changed. The transcripts of NCKX3, TRPV5-6, and PMCA1b were highly expressed in the placenta of hypoxic rat. Taken together, the expressions of renal, duodenal, and placental calcium-related proteins appear to be modulated by hypoxia-induced oxidative stress, implying that calcium-related proteins may be involved in preeclamptic oxidative stress.
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30

Shaw, G. "The uterine environment in early pregnancy in the tammar wallaby." Reproduction, Fertility and Development 8, no. 4 (1996): 811. http://dx.doi.org/10.1071/rd9960811.

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In tammar wallabies, Macropus eugenii, the uterine environment plays a key role in regulating development, because during the first two-thirds of gestation an acellular mucoid coat and shell prevent direct cell-cell contact between the endometrium and embryonic cells. This control is seen very clearly in the facultative lactational diapause of tammars. Removal of the suckled pouch young during the breeding season terminates diapause, leading to a distinct increase in metabolic activity of the embryo. By Day 4, oxidative metabolism of glucose has substantially increased, providing a four-fold increase in ATP production. By Day 5, RNA synthesis has increased. These changes are dependent on progesterone-induced changes in uterine secretions. By Day 3, there is greater progesterone secretion by the corpus luteum and, by Day 4, uterine protein synthesis has increased. The nature of the uterine regulatory factor is still not known. There are changes in some uterine proteins, but no detectable change in ionic components of the uterine fluid. Only one defined potential regulator, platelet-activating factor, has been identified, the concentration of which increased during reactivation. The influence of the steroid hormones progesterone and oestradiol on the uterus and diapausing embryo, and other changes that occur later in development, are also discussed in the present review.
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31

Mattei, Alexandra L., Mark L. Riccio, Frank W. Avila, and Mariana F. Wolfner. "Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning." Proceedings of the National Academy of Sciences 112, no. 27 (June 3, 2015): 8475–80. http://dx.doi.org/10.1073/pnas.1505797112.

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Physiological changes in females during and after mating are triggered by seminal fluid components in conjunction with female-derived molecules. In insects, these changes include increased egg production, storage of sperm, and changes in muscle contraction within the reproductive tract (RT). Such postmating changes have been studied in dissected RT tissues, but understanding their coordination in vivo requires a holistic view of the tissues and their interrelationships. Here, we used high-resolution, multiscale micro-computed tomography (CT) scans to visualize and measure postmating changes in situ in the Drosophila female RT before, during, and after mating. These studies reveal previously unidentified dynamic changes in the conformation of the female RT that occur after mating. Our results also reveal how the reproductive organs temporally shift in concert within the confines of the abdomen. For example, we observed chiral loops in the uterus and in the upper common oviduct that relax and constrict throughout sperm storage and egg movement. We found that specific seminal fluid proteins or female secretions mediate some of the postmating changes in morphology. The morphological movements, in turn, can cause further changes due to the connections among organs. In addition, we observed apparent copulatory damage to the female intima, suggesting a mechanism for entry of seminal proteins, or other exogenous components, into the female’s circulatory system. The 3D reconstructions provided by high-resolution micro-CT scans reveal how male and female molecules and anatomy interface to carry out and coordinate mating-dependent changes in the female’s reproductive physiology.
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32

Mok, Hoyin, Sharon J. Tollefson, Amy B. Podsiad, Bryan E. Shepherd, Vasiliy V. Polosukhin, Robert E. Johnston, John V. Williams, and James E. Crowe. "An Alphavirus Replicon-Based Human Metapneumovirus Vaccine Is Immunogenic and Protective in Mice and Cotton Rats." Journal of Virology 82, no. 22 (September 10, 2008): 11410–18. http://dx.doi.org/10.1128/jvi.01688-08.

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ABSTRACT Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.
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33

Fan, LQ, RC Cattley, and JC Corton. "Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor alpha." Journal of Endocrinology 158, no. 2 (August 1, 1998): 237–46. http://dx.doi.org/10.1677/joe.0.1580237.

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The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.
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34

Wallace, JM, RP Aitken, and MA Cheyne. "Effect of post-ovulation nutritional status in ewes on early conceptus survival and growth in vivo and luteotrophic protein secretion in vitro." Reproduction, Fertility and Development 6, no. 2 (1994): 253. http://dx.doi.org/10.1071/rd9940253.

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Overfeeding during early pregnancy in ewes compromises pregnancy establishment and/or embryo survival. To determine whether high feed intakes after ovulation alter the secretory dialogue between the conceptus and the endometrium, 24 embryos (8-16-cell) from ewes fed maintenance rations were synchronously transferred in singleton on Day 3 of the cycle (oestrus, Day 0) into the uterus of ewes receiving a high or low plane of nutrition from Day 0 (n = 12 ewes per group). Embryo survival and conceptus growth were assessed on Day 16. At this time, pregnancy was maintained in 11 of 12 recipient ewes per group and conceptus mass was not influenced by nutritional plane (637 +/- 48 v. 583 +/- 72 mg for high and low groups respectively). Conceptus and endometrial tissues were cultured separately for a further 24 h in vitro in the presence of [3H]leucine. There was no quantitative difference between nutritional treatments in the incorporation of radiolabel into proteins synthesized and secreted by the conceptus or endometrium. Secretion of ovine trophoblast protein-1 was also similar in both groups. Peripheral progesterone concentrations were significantly (P < 0.05) lower throughout the luteal phase in recipient ewes on high v. low intakes after ovulation. This effect was independent of ovulation rate which was 3.1 +/- 0.40 and 2.6 +/- 0.25 corpora lutea for high and low groups respectively. A high plane of nutrition after ovulation did not influence embryo survival and development in vivo or luteotrophic protein secretion in vitro despite a reduction in peripheral progesterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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35

Ciarmela, Pasquapina, Ezra Wiater, Sean M. Smith, and Wylie Vale. "Presence, Actions, and Regulation of Myostatin in Rat Uterus and Myometrial Cells." Endocrinology 150, no. 2 (February 1, 2009): 906–14. http://dx.doi.org/10.1210/en.2008-0880.

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Myostatin, a member of the TGF-β superfamily of proteins, is known to suppress skeletal muscle mass and myocyte proliferation. The muscular component of the uterus is the myometrium, a tissue that regulates its mass in response to different physiological conditions under the influence of sex steroids. Recently, our laboratory reported effects of activin-A, another TGF-β family member, on signalling and proliferation of rat uterine explants and human myometrial cell lines in culture. Here, we explore the expression, actions, and regulation of myostatin in uterine smooth muscle. Myostatin mRNA was demonstrated to be expressed in a myometrial cell line, pregnant human myometrial 1 cell line (PHM1). Functional assays showed that myostatin induced phosphorylation of Smad-2 and reduced proliferation of PHM1 number in a time and dose-dependent manner. Furthermore, myostatin activated smad-2 specific signalling pathways in rat uterine explants. To expand on our in vitro findings, we found that myostatin is expressed in rat uterus and determined that myostatin mRNA expression varies as a function of the phase of the estrous cycle. Uterine levels of myostatin peaked during late estrus and were the lowest at proestrus. Ovariectomy increased myostatin expression; estrogen treatment strongly decreased myostatin levels, whereas progesterone weakly decreased myostatin expression. In conclusion, myometrial cells are myostatin sensitive, myostatin mRNA levels are modulated in vivo in rats during the estrous cycle, and in response to steroid deprivation and replacement. Myometrial cells are myostatin-sensitive; myostatin mRNA levels are modulated in rats during the estrous cycle and in response to steroid deprivation and replacement.
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36

Awounfack, Charline Florence, Stéphane Zingué, Bruno Koumabas, Alain Brice Tueche, Charlotte Mungho Tata, Fernand-Nestor Tchuenguem Fohouo, Dieudonné Njamen, and Derek Tantoh Ndinteh. "Ethanol-Extracted Cameroonian Propolis Counteracts Tamoxifen-Induced Endometrial Hyperplasia by Modulating Apoptosis and Proliferation-Regulating Proteins in the Ovaries of Intact Wistar Rats." Evidence-Based Complementary and Alternative Medicine 2022 (April 13, 2022): 1–11. http://dx.doi.org/10.1155/2022/2684742.

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Tamoxifen is the most common adjuvant that has been widely used in the treatment of positive estrogen receptor (ER+) breast cancer for over 20 years. However, long term exposure to tamoxifen doubles the risk of endometrial cancer. The association of tamoxifen with antiproliferative substances could abrogate its side effects on the endometrium. Recently, we demonstrated that ethanol-extracted Cameroonian propolis (EECP) has chemopreventive effects on ER+ breast cancer in rats. This study evaluated the capability of EECP to counteract tamoxifen-induced endometrial hyperplasia, without altering its effect on the breast. Thirty-six rats of ∼2 months were coadministered either EECP (16.5, 50, and 150 mg/kg BW) or fulvestrant (300 μg/kg BW) and tamoxifen (10 mg/kg BW) for 8 weeks. Afterward, the relative weights and histomorphometry of the uterus, vagina, ovaries, and mammary gland were assessed. The expression of some proteins of proliferation (PCNA), angiogenesis (VEGF), and apoptosis (Bax, Bcl-2, and caspase-3) was measured by immunohistochemistry. Rats that received only tamoxifen had endometrial hyperplasia compared to normal rats. EECP and fulvestrant protected the rats against tamoxifen-induced endometrial hyperplasia. A significant decrease in uterine wet weight ( p < 0.01 ); endometrial height ( p < 0.001 ); and expression of PCNA, Bcl-2, and VEGF proteins as well as a significant increase in the expression of Bax and caspase-3 proteins was observed in the EECP group compared to the Tamox group. EECP did not change the effects of tamoxifen on the breast. In summary, Cameroonian propolis which is efficacious in preventing breast cancer can also be a good complementary medicine to prevent tamoxifen-induced endometrial cancer in tamoxifen users.
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37

Soares, J. M., C. da S. Ferreira, E. C. Baracat, K. C. Carvalho, A. P. R. Paiotti, C. T. F. Oshima, C. C. Maganhin, and M. de J. Simões. "M044 EFFECTS OF MELATONIN ON PRO APOPTOTIC GENES AND PROTEINS EXPRESSION IN THE UTERUS OF RATS EXPOSED TO CONTINUOUS LIGHT." International Journal of Gynecology & Obstetrics 119 (October 2012): S545. http://dx.doi.org/10.1016/s0020-7292(12)61238-7.

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38

Zervos, A. S., J. Hope, and W. H. Evans. "Preparation of a gap junction fraction from uteri of pregnant rats: the 28-kD polypeptides of uterus, liver, and heart gap junctions are homologous." Journal of Cell Biology 101, no. 4 (October 1, 1985): 1363–70. http://dx.doi.org/10.1083/jcb.101.4.1363.

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A procedure for the preparation of a gap junction fraction from the uteri of pregnant rats is described. The uterine gap junctions, when examined by electron microscopy of thin sections and in negatively stained preparations, were similar to gap junctions isolated from heart and liver. Major proteins of similar apparent molecular weight (Mr 28,000) were found in gap junction fractions isolated from the uterus, heart, and liver, and were shown to have highly homologous structures by two-dimensional mapping of their tryptic peptides. An Mr 10,000 polypeptide, previously deduced to be a proteolytic product of the Mr 28,000 polypeptide of rat liver (Nicholson, B. J., L. J. Takemoto, M. W. Hunkapiller, L. E. Hood, and J.-P. Revel, 1983, Cell, 32:967-978), was also studied and shown by chymotryptic mapping to be homologous in the uterine, heart, and liver gap junction fractions. An antibody raised in rabbits to a synthetic peptide corresponding to an amino-terminal sequence of the liver gap junction protein recognized Mr 28,000 proteins in the three tissues studied, showing that the proteins shared common antigenic determinants. These results indicate that gap junctions are biochemically conserved plasma membrane specializations. The view that gap junctions are tissue-specific plasma membrane organelles based on previous comparisons of Mr 26,000-30,000 polypeptides is not sustained by the present results.
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39

Cheng, Yu-Shen, Hung-Hsun Yen, Chung-Yen Chang, Wei-Chih Lien, Shu-Hung Huang, Su-Shin Lee, Lin Wang та Hui-Min David Wang. "Adipose-Derived Stem Cell-Incubated HA-Rich Sponge Matrix Implant Modulates Oxidative Stress to Enhance VEGF and TGF-β Secretions for Extracellular Matrix Reconstruction In Vivo". Oxidative Medicine and Cellular Longevity 2022 (17 січня 2022): 1–17. http://dx.doi.org/10.1155/2022/9355692.

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This study demonstrated both adipose-derived stem cells (ASCs) in vitro and in vivo combined with three-dimensional (3D) porous sponge matrices on implant wound healing. Sponge matrices were created from hyaluronic acid (HA), collagen (Col), and gelatin (Gel), constructing two types: HA-L (low content) and HA-H (high content), to be cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Fourier transform infrared spectroscopy method verified carboxyl groups of HA and amino groups of Col and Gel reacting between the raw materials and scaffolds to identify the successive cross-linking. The swelling ratios of two types of sponge matrices were analyzed by water absorption capabilities, and the results displayed both over 30-fold dry scaffold weight enhancements. In biodegradation tests, matrices were hydrolyzed over time by three cutaneous enzymes, hyaluronidase, lysozyme, and collagenase I. ASCs from rats were cultured within the HA-H scaffold, demonstrating higher antioxidative abilities and secretions on related genes and proteins compared to the other two groups. The ASC HA-H matrix promoted cell proliferation to stimulate capillary angiogenesis inducer secretions, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). In vivo histological examinations showed ASCs from implanted HA-H implant transported into the subcutis, and rat skin cells also infiltrated into the original matrix zone to increase the extracellular matrix (ECM) reconstructions. Our experimental data revealed that the ASC HA-H sponge implant was effective in improving wound repair.
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40

Rider, Virginia, Alex Talbott, Anuradha Bhusri, Zach Krumsick, Sierra Foster, Joshua Wormington, and Bruce F. Kimler. "WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell proliferation." Journal of Endocrinology 229, no. 2 (May 2016): 197–207. http://dx.doi.org/10.1530/joe-15-0523.

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Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3β (GSK-3β) and stimulating β-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidate Wnt genes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg/daily) rats, and progesterone-pretreated rats given a single dose (0.2µg) of estradiol. The spatial distribution of the WNT proteins was determined in the uteri after the same treatments. Wnt5a increased in response to progesterone and the protein emerged in the periluminal stromal cells of progesterone-pretreated rat uteri. To investigate whether WNT5A was required for proliferation, uterine stromal cell lines were stimulated with progesterone (1µM) and fibroblast growth factor (FGF, 50ng/mL). Proliferating stromal cells expressed a two-fold increase in WNT5A protein at 12h post stimulation. Stimulated stromal cells were cultured with actinomycin D (25µg/mL) to inhibit new RNA synthesis. Relative Wnt5a expression increased at 4 and 6 h of culture, suggesting that progesterone plus FGF preferentially increased Wnt5a mRNA stability. Knockdown of Wnt5a in uterine stromal cell lines inhibited stromal cell proliferation and decreased Wnt5a mRNA. The results indicate that progesterone initiates and synchronizes uterine stromal cell proliferation by increasing WNT5A expression and signaling.
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41

Kim, J. H., K. C. Choi, and E. B. Jeung. "186 DUODENAL AND RENAL TRANSIENT RECEPTOR POTENTIAL VANILLOID 6 APPEAR TO BE DISTINCTLY REGULATED BY SEX STEROID HORMONES, ESTROGEN AND PROGESTERONE, IN IMMATURE FEMALE RATS." Reproduction, Fertility and Development 21, no. 1 (2009): 192. http://dx.doi.org/10.1071/rdv21n1ab186.

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Calcium-related proteins include transient receptor potential vanilloid (TRPV) 5 and 6, plasma membrane calcium-ATPase 1b (PMCA1b), and calbindin-D9k and -D28k. The TRPV6 is a major calcium channel located in the apical and basolateral membranes of cell and distributed widely in many other organs, especially in the exocrine tissues such as intestine and uterus. TRPV6s are generally regulated by vitamin D, a dietary calcium ion and hormone. In particular, uterine TRPV6 appears to be affected by sex steroid hormones, which are altered according to estrous cycle and pregnancy. In order to discover the effect of sex steroid hormones on the regulation of TRPV6, we examined the expression of TRPV6 mRNA by using RT-PCR and real-time PCR, and protein expression of TRPV6 by immunohistochemistry (IHC) in the uterus, duodenum, and kidney. To evaluate the effect(s) of sex steroid hormones on its uterine, duodenal, and renal regulation, 17β-estradiol [E2; 40 μg kg–1 of body weight (bw)] and/or progesterone (P4; 4 mg kg–1 of bw) or vehicle (n = 6/each group) were subcutaneously injected into Sprague-Dawley immature female rats (14 days old, n = 24 in total) for 3 days. As a result, the treatments of immature rats with E2 or P4 increased TRPV6 mRNA for calcium function or regulation in the uterus of immature rats. To confirm the specificity of E2 or P4 through their receptors, we treated the immature rats (extra n = 24 in total) with an estrogen receptor-antagonist, ICI 182,780 (ICI; 30 μg kg–1 of bw), and/or progesterone receptor antagonist, RU 486 (10 mg kg–1 of bw), at 3 days prior to E2 or P4 injection. Consequently, an increase in TRPV6 mRNA was observed in the following 2 treatments; ICI plus E2/P4 and E2/P4 alone. In IHC, we further observed that the expression of duodenal TRPV6 was increased by E2 or P4 and E2 or P4 plus ICI, while no difference was observed in renal TRPV6 by the treatments of sex steroid hormones. In conclusion, these results indicate that the expressions of uterine and duodenal TRPV6 may be induced by E2 and P4, but its renal expression may not be controlled by these steroids.
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42

Kim, Hoe-Jin, Geun-Shik Lee, Youn-Kyu Ji, Kyung-Chul Choi, and Eui-Bae Jeung. "Differential expression of uterine calcium transporter 1 and plasma membrane Ca2+ ATPase 1b during rat estrous cycle." American Journal of Physiology-Endocrinology and Metabolism 291, no. 2 (August 2006): E234—E241. http://dx.doi.org/10.1152/ajpendo.00434.2005.

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Calcium-related proteins include the calcium transporters 1 and 2 (CaT1 and CaT2), plasma membrane Ca2+-ATPase 1b (PMCA1b), and calbindin-D9k and -D28k. The expression of CaT1 and PMCA1b and their potential roles in the uterine tissue remain to be clarified. Thus, in the present study, the expression patterns of CaT1 and PMCA1b were examined to predict their roles in rat uterus during the estrous cycle. Both CaT1 and PMCA1b mRNAs were detected in rat uterus. Uterine CaT1 mRNA was highly expressed at diestrus compared with proestrus, whereas PMCA1b expression was not altered during the estrus cycle. To evaluate the sex steroids involved in uterine CaT1 mRNA regulation, 17β-estradiol (E2) and/or progesterone (P4) were injected into immature rats. Treatment with P4 or E2 plus P4 resulted in an increase in CaT1 mRNA, but a synergetic effect of E2 plus P4 was not detected. Uterine CaT1 mRNA was induced by P4 in a time- and dose-dependent manner, with maximal transcript detected 12 h after the final P4 injection. Treatment with RU486, a progesterone receptor (PR) antagonist, completely blocked P4-induced CaT1 mRNA, indicating that P4 regulates CaT1 mRNA expression via a PR-mediated pathway. In addition, CaT1 mRNA was expressed in uterine endometrium and glandular endometrium at diestrus in P4-treated rats. Together, these results suggest that CaT1 is regulated by P4 at diestrus via a PR-dependent pathway.
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43

Shpakov, A. O., K. V. Derkach, and V. M. Bondareva. "A decrease of sensitivity of adenylyl cyclase and heterotrimeric g-proteins to chorionic gonadotropin and peptide hormones action in the tissues of reproductive system of the rats in the condition of experimental type 2 diabetes." Biomeditsinskaya Khimiya 56, no. 6 (2010): 700–709. http://dx.doi.org/10.18097/pbmc20105606700.

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Patients with different forms of the diabetes, particularly with insulin-independent type 2 diabetes have a wide spectrum of the disturbances of the functions of reproductive system. It is supposed that the main reason of these disturbances is altered sensitivity of reproductive system tissues to regulatory action of hormones. The aim of the work was the identification of the changes in functioning of human chorionic gonadotropin (hCG) - and peptide hormones-sensitive adenylyl cyclase system (ACS) in the ovary, testes and uterus of rats with neonatal streptozotocin (STZ) diabetes that is similar to the type 2 diabetes in humans. The effects of hCG, PACAP-38 and relaxin, realizing their effects via G-protein of the stimulatory type (Gs), and somatostatin, acting via G-protein of the inhibitory type (Gi), on adenylyl cyclase (AC) activity and the GTP binding of the G-proteins were studied. Regulatory effects of hCG and PACAP-38 decreased in the ovary and testes of rats with STZ type 2 diabetes, while the effects of somatostatin decreased in all investigated tissues (in a considerable extent in the uterus). This expressed in the weakening of hormonal effects on AC activity, stimulating in the case of hCG and PACAP-38 and inhibiting in the case of somatostatin, and in the decrease of stimulation of the GTP binding by the hormones. At the same time a significant decrease of ACS sensitivity to relaxin in the tissues of diabetic rats was not found. Data obtained suggest that the key reason of the disturbances of reproductive functions in experimental type 2 diabetes is the decrease of ACS sensitivity to the hormones, such as hCG, PACAP-38 and somatostatin, that play a important role in functioning of reproductive system.
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44

Mokhtar, Mohd Helmy, Nelli Giribabu, and Naguib Salleh. "Testosterone Decreases the Number of Implanting Embryos, Expression of Pinopode and L-selectin Ligand (MECA-79) in the Endometrium of Early Pregnant Rats." International Journal of Environmental Research and Public Health 17, no. 7 (March 29, 2020): 2293. http://dx.doi.org/10.3390/ijerph17072293.

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Testosterone could have adverse effect on fertility. In this study, we hypothesized that this hormone could reduce the number of embryo implantations via affecting the normal endometrium ultrastructure and expression of endometrial proteins involved in implantation. Therefore, the aims were to identify these adverse testosterone effects. Methods: Intact pregnant rats were given 250 or 500 µg/kg/day testosterone for three days, beginning from day 1 of pregnancy. Rats were euthanized either at day 4 to analyze the ultra-structural changes in the endometrium and expression and distribution of MECA-79 protein, or at day 6 to determine the number of implantation sites. Results: Administration of 500 µg/kg/day testosterone suppresses endometrial pinopodes development and down-regulates expression and distribution of MECA-79 protein in the uterus. In addition, the number of implantation sites were markedly decreased. Conclusions: Changes in endometrial ultrastructure and expression of implantation protein in the endometrium in early pregnancy period could be the reason for failure of embryo implantation under testosterone influence.
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45

Lin, Chen, Hong He, Ning Cui, Zongli Ren, Minglin Zhu, and Raouf A. Khalil. "Decreased uterine vascularization and uterine arterial expansive remodeling with reduced matrix metalloproteinase-2 and -9 in hypertensive pregnancy." American Journal of Physiology-Heart and Circulatory Physiology 318, no. 1 (January 1, 2020): H165—H180. http://dx.doi.org/10.1152/ajpheart.00602.2019.

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Normal pregnancy involves extensive remodeling of uterine and spiral arteries and matrix metalloproteinases (MMPs)-mediated proteolysis of extracellular matrix (ECM). Preeclampsia is characterized by hypertension in pregnancy (HTN-Preg) and intrauterine growth restriction (IUGR) with unclear mechanisms. Initial faulty placentation and reduced uterine perfusion pressure (RUPP) could release cytoactive factors and trigger an incessant cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent and depth of uterine vascularization and the proteolytic enzymes and ECM proteins involved are unclear. We hypothesized that HTN-Preg involves decreased uterine vascularization and arterial remodeling by MMPs and accumulation of ECM collagen. Blood pressure (BP) and fetal parameters were measured in normal Preg rats and RUPP rat model, and the uteri were assessed for vascularity, MMP levels, and collagen deposition. On gestational day 19, BP was higher, and the uterus weight, litter size, and pup weight were reduced in RUPP vs. Preg rats. Histology of uterine tissue sections showed reduced number (5.75 ± 0.95 vs. 11.50 ± 0.87) and size (0.05 ± 0.01 vs. 0.12 ± 0.02 mm2) of uterine spiral arterioles in RUPP vs. Preg rats. Immunohistochemistry showed localization of endothelial cell marker cluster of differentiation 31 (CD31) and smooth muscle marker α-actin in uterine arteriolar wall and confirmed decreased number/size of uterine arterioles in RUPP rats. The cytotrophoblast marker cytokeratin-7 showed less staining and invasion of spiral arteries in the deep decidua of RUPP vs. Preg rats. Uterine arteries showed less expansion in response to increases in intraluminal pressure in RUPP vs. Preg rats. Western blot analysis, gelatin zymography, and immunohistochemistry showed decreases in MMP-2 and MMP-9 and increases in the MMP substrate collagen-IV in uterus and uterine arteries of RUPP vs. those in Preg rats. The results suggest decreased number, size and expansiveness of spiral and uterine arteries with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg. Decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could be contributing mechanisms to uteroplacental ischemia in HTN-Preg and preeclampsia. NEW & NOTEWORTHY Preeclampsia is a pregnancy-related disorder in which initial inadequate placentation and RUPP cause the release of cytoactive factors and trigger a ceaseless cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent/depth of uterine vascularization and the driving proteolytic enzymes and ECM proteins are unclear. This study shows decreased number, size, and expansiveness of uterine spiral arteries, with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg rats. The decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could contribute to progressive uteroplacental ischemia in HTN-Preg and preeclampsia.
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46

Ochoa, AL, NA Mitchner, CD Paynter, RE Morris, and N. Ben-Jonathan. "Vascular endothelial growth factor in the rat pituitary: differential distribution and regulation by estrogen." Journal of Endocrinology 165, no. 2 (May 1, 2000): 483–92. http://dx.doi.org/10.1677/joe.0.1650483.

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Vascular endothelial growth factor (VEGF), an endothelial cell mitogen and permeability factor, participates in tumor angiogenesis, but less is known about its regulation or function in normal vascular homeostasis. In the uterus, which undergoes cyclic changes in its vasculature, VEGF is induced by estrogen. Since the pituitary gland contains highly permeable capillaries and is estrogen-responsive, our objectives were to localize VEGF expression within the pituitary and to determine whether it is regulated by estrogen in both the pituitary and the somatolactotrope cell line, GH(3). Ovariectomized rats were injected with estradiol, and pituitaries and uteri were subjected to in situ hybridization or quantitative reverse transcription-polymerase chain reaction (RT-PCR). VEGF expression was strong and punctate in the neural lobe, weaker and diffuse in the anterior lobe and undetectable in the intermediate lobe. Two VEGF isoforms, 164 and 120, were detected in all tissues. In the posterior pituitary, VEGF expression was 3- to 6-fold higher than in the anterior pituitary or uterus and was unaltered by estrogen. In contrast, anterior pituitary VEGF was induced by estrogen within 1 h, peaked at 3 h, and returned to basal levels by 24 h. Similar dynamics, albeit 10-fold higher, were seen in the uterus. Translated VEGF proteins were detected by Western blot in both the anterior pituitary and uterus. GH(3) cells also showed a dose- and time-dependent induction of VEGF expression by estrogen. In conclusion: (1) VEGF expression is higher in the neural lobe than in the anterior lobe and is undetectable in the intermediate lobe, (2) the expression of VEGF164 and VEGF120 is rapidly upregulated by estrogen in the anterior pituitary but is unchanged in the posterior pituitary, and (3) the pituitary lactotrope cell line, GH(3), also increases VEGF expression in response to estradiol.
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47

Suzuki, Takahiro, and Koichi Takimoto. "Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy." American Journal of Physiology-Endocrinology and Metabolism 288, no. 2 (February 2005): E335—E341. http://dx.doi.org/10.1152/ajpendo.00250.2004.

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Regulation of voltage-gated K+ (Kv) channel expression may be involved in controlling contractility of uterine smooth muscle cells during pregnancy. Functional expression of these channels is not only controlled by the levels of pore-forming subunits, but requires their association with auxiliary subunits. Specifically, rapidly inactivating Kv current is prominent in myometrial cells and may be carried by complexes consisting of Kv4 pore-forming and KChIP auxiliary subunits. To determine the molecular identity of the channel complexes and their changes during pregnancy, we examined the expression and localization of these subunits in rat uterus. RT-PCR analysis revealed that rat uterus expressed all three Kv4 pore-forming subunits and KChIP2 and -4 auxiliary subunits. The expression of mRNAs for these subunits was dynamically and region selectively regulated during pregnancy. In the corpus, Kv4.2 mRNA level increased before parturition, whereas the expression of Kv4.1 and Kv4.3 mRNAs decreased during pregnancy. A marked increase in KChIP2 mRNA level was also seen at late gestation. In the cervix, the expression of all three pore-forming and two auxiliary subunit mRNAs increased at late gestation. Immunoprecipitaton followed by immunoblot analysis indicated that Kv4.2-KChIP2 complexes were significant in uterus at late pregnancy. Kv4.2- and KChIP2-immunoreactive proteins were present in both circular and longitudinal myometrial cells. Finally, Kv4.2 and KChIP2 mRNA levels were similarly elevated in pregnant and nonpregnant corpora of one side-conceived rats. These results suggest that diffusible factors coordinate the pregnancy-associated changes in molecular compositions of myometrial Kv4-KChIP channel complexes.
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48

Spencer, Thomas E., Greg A. Johnson, Fuller W. Bazer, and Robert C. Burghardt. "Implantation mechanisms: insights from the sheep." Reproduction 128, no. 6 (December 2004): 657–68. http://dx.doi.org/10.1530/rep.1.00398.

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Implantation in all mammals involves shedding of the zona pellucida, followed by orientation, apposition, attachment and adhesion of the blastocyst to the endometrium. Endometrial invasion does not occur in domestic ruminants; thus, definitive implantation is achieved by adhesion of the mononuclear trophoblast cells to the endometrial lumenal epithelium (LE) and formation of syncytia by the fusion of trophoblast binucleate cells with the LE. This review highlights new information on mechanisms regulating the implantation cascade in sheep. The embryo enters the uterus on day 4 at the morula stage of development and then develops into a blastocyst by day 6. The blastocyst sheds the zona pellucida (day 8), elongates to a filamentous form (days 11–16), and adheres to the endometrial LE (day 16). Between days 14 and 16, the binucleate cells begin to differentiate in the trophoblast and subsequently migrate and fuse with the endometrial LE to form syncytia. Continuous exposure of the endometrium to progesterone in early pregnancy downregulates the progesterone receptors in the epithelia, a process which is associated with loss of the cell-surface mucin MUC1 and induction of several secreted adhesion proteins. Recurrent early pregnancy loss in the uterine gland knockout ewe model indicates that secretions of the endometrial epithelia have a physiologic role in blastocyst elongation and implantation. A number of endometrial proteins have been identified as potential regulators of blastocyst development and implantation in sheep, including glycosylated cell adhesion molecule 1 (GlyCAM-1), galectin-15, integrins and osteopontin. The epithelial derived secreted adhesion proteins (GlyCAM-1, galectin-15 and osteopontin) are expressed in a dynamic temporal and spatial manner and regulated by progesterone and/or interferon tau, which is the pregnancy recognition signal produced by the trophoblast during blastocyst elongation. The noninvasive and protracted nature of implantation in domestic animals provides valuable opportunities to investigate fundamental processes of implantation that are shared among all mammals. Understanding of the cellular and molecular signals that regulate uterine receptivity and implantation can be used to diagnose and identify causes of recurrent pregnancy loss and to improve pregnancy outcome in domestic animals and humans.
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49

Salleh, Naguib, Abu Sadat Md Sayem, Nelli Giribabu, and Si Lay Khaing. "Expression of proteins related to thyroid hormone function in the uterus is down‐regulated at the day of implantation in hypothyroid pregnant rats." Cell Biology International 43, no. 5 (March 12, 2019): 486–94. http://dx.doi.org/10.1002/cbin.11114.

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50

Kitterman, Joseph A., Cheryl J. Chapin, Jeff N. Vanderbilt, Nicolas F. M. Porta, Louis M. Scavo, Leland G. Dobbs, Robert Ertsey, and Jon Goerke. "Effects of oligohydramnios on lung growth and maturation in the fetal rat." American Journal of Physiology-Lung Cellular and Molecular Physiology 282, no. 3 (March 1, 2002): L431—L439. http://dx.doi.org/10.1152/ajplung.00161.2001.

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Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA ( P < 0.05) and protein ( P < 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter ( P < 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells.
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