Добірка наукової літератури з теми "Placenta, glucose, BPA"

This work aims to clarify the effect of dietary supplementation with Bisphenol A (BPA), a chemical widely present in beverage and food containers, on placental glucose transfer and pregnancy outcome. The study was performed on female Sprague Dawley rats fed with a diet containing BPA (2.5, 25 or 250 μg/Kg/day) for a period of a month (virgin state) plus 20 days during pregnancy. Western blot analysis and immunohistochemistry were performed in placental tissues for glucose type 1 transporter (GLUT1). Furthermore, human trophoblast, HTR8-SV/neo cells, were used to evaluate the effect of BPA on glucose transport and uptake. Studies in rats showed that food supplementation with BPA, produces a higher fetal weight (FW) to placenta weight (PW) ratio at the lowest BPA concentration. Such low concentrations also reduced maternal weight gain in late pregnancy and up-regulated placental expression of GLUT1. Treatment of HTR8-SV/neo with the non-toxic dose of 1 nM BPA confirmed up-regulation of GLUT1 expression and revealed higher activity of the transporter with an increase in glucose uptake and GLUT1 membrane translocation. Overall, these results indicate that prenatal exposure to BPA affects pregnancy and fetal growth producing changes in the placental nutrients-glucose transfer.

Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance and eventual pancreatic β-cell dysfunction, resulting in persistent high blood glucose levels. Endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) are currently under scrutiny as they are implicated in the development of metabolic diseases, including T2DM. BPA is a pervasive EDC, being the main constituent of polycarbonate plastics. It can enter the human body by ingestion, through the skin, and cross from mother to offspring via the placenta or breast milk. BPA is a xenoestrogen that alters various aspects of beta cell metabolism via the modulation of oestrogen receptor signalling. In vivo and in vitro models reveal that varying concentrations of BPA disrupt glucose homeostasis and pancreatic β-cell function by altering gene expression and mitochondrial morphology. BPA also plays a role in the development of insulin resistance and has been linked to long-term adverse metabolic effects following foetal and perinatal exposure. Several epidemiological studies reveal a significant association between BPA and the development of insulin resistance and impaired glucose homeostasis, although conflicting findings driven by multiple confounding factors have been reported. In this review, the main findings of epidemiological and functional studies are summarised and compared, and their respective strengths and limitations are discussed. Further research is essential for understanding the exact mechanism of BPA action in various tissues and the extent of its effects on humans at environmentally relevant doses.

Dietary exposure to Bisphenol A (BPA), an industrial chemical present in food containers, affects nutrient metabolism in the myocardium of offspring during intrauterine life. Using a murine model, we observed that fetal hearts from mothers exposed to BPA (2.5 μg/kg/day) for 20 days before mating and for all of the gestation had decreased expression of glucose transporter-1 (GLUT1), the principal sugar transporter in the fetal heart, and increased expression of fatty acid cluster of differentiation 36 transporter (CD36), compared to control fetuses from vehicle-treated mothers. We confirmed the suppression of GLUT1 by exposing fetal heart organotypic cultures to BPA (1 nM) for 48 h but did not detect changes in CD36 compared to controls. During pregnancy, the placenta continuously releases extracellular vesicles such as exosomes into fetal circulation. These vesicles influence the growth and development of fetal organs. When fetal heart cultures were treated with cord blood-derived exosomes isolated from BPA-fed animals, GLUT1 expression was increased by approximately 40%. Based on our results, we speculate that exosomes from cord blood, in particular placenta-derived nanovesicles, could contribute to the stabilization of the fetal heart metabolism by ameliorating the harmful effects of BPA on GLUT1 expression.

The placenta exchanges vital factors, including oxygen, carbon dioxide, copper, iron, calcium cations, and glucose, which are essential to fetal growth. Each molecule is transferred by specific receptors that are located at the cell membrane or in the cytoplasm. Copper, iron, calcium cations, and glucose transfer genes are regulated by estrogens, vitamin D, and human placental lactogen. Regulations of these receptors depend on pregnancy time length and maternal and fetal nutrient environment with various pathways. Some synthetic plastics known as endocrine disrupting chemicals (EDC) have a similar structure to reproductive hormones such as estrogens. Thus, these substances have a potential effect on the expression of genes which are regulated by estrogens or progesterone by interfering their pathways. Having an estrogenic property, EDC interact with oestrogen receptors and elevate or decrease the expression of target genes which are responsible for transporting essential molecules such as copper, iron, and calcium. To examine the effects of EDC exposure during pregnancy, we conducted an in vitro model study using the BeWo human trophoblast cell line. The BeWo cell was treated with well-known EDC, octyl-phenol (OP), nonyl-phenol (NP), and bisphenol A (BPA) in a dose-dependent manner (10–7, 10–6, and 10–5 M) for 24 h. The expression of copper (CTR1, ATP7A), iron (IREG1, HEPH), and calcium transporting genes (PMCA1, TRPV6), were measured by real-time RT–PCR and Western blot. The expression of copper, iron, and calcium transporting genes were elevated in a dose-dependent manner by all well-known EDC, including OP, NP, and BPA, as well as E2. To unveil the mechanism of these elevations of ionic transporting genes, an ERE promoter study will be needed. Taken together, essential cation transporting genes in placenta are modulated by EDC.

Maternal obesity during pregnancy is often characterized by fetal macrosomia but it can also result in fetal growth restriction in a subset of pregnancies. We hypothesized that mechanisms of this growth restriction may include adverse effects of maternal high fat (HF) intake on placental growth and function. Female rats (100 days old) were time-mated and randomly assigned to either a control (Con) or HF diet ad libitum throughout gestation. At E21, dams were killed; litter size and fetal and placental weights were recorded and maternal and fetal samples collected for further analyses. The HF diet resulted in a 54% increase in maternal body weight gain during gestation. In contrast, male and female fetal weights were reduced in HF pregnancies (P < 0.05), as were the weights of the junctional zone of the placenta (P = 0.013), whereas labyrinth zone weights were unaffected. The HF diet increased maternal and fetal plasma leptin levels (P < 0.05), but maternal and fetal insulin and fetal glucose levels were unaffected. Labyrinthine expression of PPARγ and total VEGFa mRNA, both markers of placental vascular development, were unaffected by consumption of the HF diet in placentas of male and female fetuses. Furthermore, maternal HF nutrition did not alter phosphorylated protein levels of either mammalian target of rapamycin or its downstream signaling factor eIF4E binding protein 1 (4E-BP1). These data show that in the rat, maternal HF nutrition results in fetal and placental junctional zone growth restriction, maternal and fetal hyperleptinemia but did not alter gene expression of markers of placental vascular development.

Bisphenol A (BPA) is a synthetic phenol extensively used in the manufacture of polycarbonate plastics and epoxy resins and a component of liquid and food storages. Among health disorders potentially attributed to BPA, the effects on metabolism have been especially studied. BPA represents a hazard in prenatal life because of its presence in tissues and fluids during pregnancy. Our recent study in rats fed with BPA showed a placental increase in glucose type 1 transporter (GLUT-1), suggesting a higher uptake of glucose. However, the role of BPA on GLUT transporters in pregnant women with metabolic dysfunction has not yet been investigated. In this study, placental tissue from 26 overweight (OW) women and 32 age-matched normal weight (NW) pregnant women were examined for expression of GLUT1 and GLUT4. Placental explants from OW and NW mothers were exposed to BPA 1 nM and 1 μM and tested for GLUTs expression. The data showed a different response of placental explants to BPA in GLUT1 expression with an increase in NW mothers and a decrease in OW ones. GLUT4 expression was lower in the explants from OW than NW mothers, while no difference was showed between OW and NW in placental biopsies for any of the transporters.

Abstract L-Proline (proline) in amniotic fluid was markedly increased during pregnancy in both pigs and sheep. However, in vivo data to support a beneficial effect of proline on fetal survival are not available. In this study, pregnant C57BL/6J mice were fed a purified diet supplemented with or without 0.50% proline from embryonic day 0.5 (E0.5) to E12.5 or term. Results indicated that dietary supplementation with proline to gestating mice enhanced fetal survival, reproductive performance, the concentrations of proline, arginine, aspartic acid, and tryptophan in plasma and amniotic fluid, while decreasing the concentrations of ammonia and urea in plasma and amniotic fluid. Placental mRNA levels for amino acid transporters, including Slc36a4, Slc38a2, Slc38a4, Slc6a14, and Na+/K+ ATPase subunit-1α (Atp1a1), fatty acid transporter Slc27a4, and glucose transporters Slc2a1 and Slc2a3, were augmented in proline-supplemented mice, compared with the control group. Histological analysis showed that proline supplementation enhanced labyrinth zone in the placenta of mice at E12.5, mRNA levels for Vegf, Vegfr, Nos2, and Nos3, compared with the controls. Western blot analysis showed that proline supplementation increased protein abundances of phosphorylated (p)-mTORC1, p-ribosomal protein S6 kinase (p70S6K), and p-eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), as well as the protein level of GCN2 (a negative regulator of mTORC1 signaling). Collectively, our results indicate a novel functional role of proline in improving placental development and fetal survival by enhancing placental nutrient transport, angiogenesis, and protein synthesis.

In this study, we determined rates of lysine metabolism in fetal sheep during chronic hypoglycemia and following euglycemic recovery and compared results with normal, age-matched euglycemic control fetuses to explain the adaptive response of protein metabolism to low glucose concentrations. Restriction of the maternal glucose supply to the fetus lowered the net rates of fetal (umbilical) glucose (42%) and lactate (36%) uptake, causing compensatory alterations in fetal lysine metabolism. The plasma lysine concentration was 1.9-fold greater in hypoglycemic compared with control fetuses, but the rate of fetal (umbilical) lysine uptake was not different. In the hypoglycemic fetuses, the lysine disposal rate also was higher than in control fetuses due to greater rates of lysine flux back into the placenta and into fetal tissue. The rate of CO2 excretion from lysine decarboxylation was 2.4-fold higher in hypoglycemic than control fetuses, indicating greater rates of lysine oxidative metabolism during chronic hypoglycemia. No differences were detected for rates of fetal protein accretion or synthesis between hypoglycemic and control groups, although there was a significant increase in the rate of protein breakdown ( P < 0.05) in the hypoglycemic fetuses, indicating small changes in each rate. This was supported by elevated muscle specific ubiquitin ligases and greater concentrations of 4E-BP1. Euglycemic recovery after chronic hypoglycemia normalized all fluxes and actually lowered the rate of lysine decarboxylation compared with control fetuses ( P < 0.05). These results indicate that chronic hypoglycemia increases net protein breakdown and lysine oxidative metabolism, both of which contribute to slower rates of fetal growth over time. Furthermore, euglycemic correction for 5 days returns lysine fluxes to normal and causes an overcorrection of lysine oxidation.

Decreased protein breakdown in pregnant women results in lower concentration of methionine (Met) in plasma, causing pregnancy-related metabolic disturbance. Its dipeptide methionyl-methionine (Met-Met) may exert positive influence in fetal development. This study mainly investigated whether Met-Met can be used as part of free Met to promote reproductive outcomes in mice and the underlying mechanisms. Met-deficient pregnant mice were treated with Met alone or with Met-Met during pregnancy. Daily intraperitoneal injection of 35% dietary Met in pregnant mice was the best dose among the 15–45% doses. Embryo development and newborn birth weight were enhanced when 25% of the Met in the 35% Met group was replaced with Met-Met. Met-Met replacement had higher plasma insulin, glucose, and free amino acids (AA) concentrations. Besides, in the placenta, the AA transporter mRNA abundances and peptide transporters (PhT1 and PepT1) protein levels were higher in Met-Met treatment group. Moreover, Met-Met increased 4E-BP1, S6K1 and AKT/mTOR phosphorylation. These results suggest that Met-Met could be used as a partial source of Met to promote reproductive outcomes in Met-restricted pregnant mice, which might be mediated by promoting nutrient availability and activating AKT/mTOR-mediated signaling pathway.

Glucose is one of the main nutrients for fetal development. Nevertheless, a significant gluconeogenesis ability by the fetus has not been reported, therefore the fetal glucose homeostasis depends on the ability of the placenta to carry out glucose from the maternal blood and to transport it to fetal tissues by means of specific transport molecules, known as GLUTs. Several conditions contribute to an imbalance in fetal glucose homeostasis, including incorrect mother feeding, maternal obesity, maternal type II diabetes and/or pregnancy complications. These conditions can affect the normal development of the fetus by affecting glucose transfer through the placenta. Nowadays it is known that environmental contaminants are able to impair placental glucose homeostasis compromising fetal development. These substances include synthetic chemicals with estrogen-like behavior referred as to Endocrine Disrupting Chemicals (EDCs), of which Bisphenol A represents one of the most important for its wide distribution in many daily-use products. However, in which way these two possible maternal perturbations (altered glucose supply and BPA exposure) are able to interfere with placental glucose uptake and how this interference may reflect on an incorrect fetal development has to be elucidated. For this purpose, this study aimed to clarify the effect of such perturbations on human placental glucose homeostasis. The studies were conducted in vitro, in human placental cell line, and in vivo, in rat placenta and fetal heart. The results showed that both, altered glucose supply and BPA exposure, influence human and rat placental glucose transport. Moreover, the in vivo study revealed that BPA disruption on placental glucose homeostasis compromise fetal rat heart development.

En Medicina, el área de aplicación de Ginecología, la ciencia de la mujer condensa el estudio de las enfermedades frecuentes y graves, el diagnóstico, detección de los factores de riesgo y establecer mecanismos de prevención, prescribir los tratamientos médicos y quirúrgicos de las enfermedades del sis- tema reproductor femenino, entiéndase, todo lo relacionado con la vagina, las mamas, el útero y los ovarios. Durante el siglo XX, motivado por el crecimiento acelerado del conocimien- to científico y médico, se acrecienta la toma de conciencia del rol que le co- rresponde desempeñar a la medicina en el sector de la salud y la protección de la mujer embarazada. Los problemas del trato genital femenino cuando se asumen como responsabilidad de los ginecólogos, quienes incluyeron dentro del proceso de auscultación, diagnóstico y tratamiento aspectos fisiológicos y endocrinos. Las barreras de la formación académica se fueron difuminando y los ginecó- logos y obstetras comenzaron a estrechar su campo laboral y como resultante se constituyó la Ginecobstetricia. En el marco de estas reflexiones, surge la idea de la presentación de un tex- to titulado Ginecología – Obstetricia, mediante el cual se pretende hacer una contribución real a nivel teórico que permita apoyar a profesionales y estu- diantes en el área de salud humana, básicamente en algunas de las patologías o complicaciones médicas asociadas al embarazo, y tratadas por la especialidad obstétrica, así mismo, se abordan dos temas (1 y 2) de conocimiento general. Cabe indicar que el texto no pretende abordar la vasta información o literatura que sobre los temas se han tratado. El libro ha sido estructurado bajo el perfil de diez (10) temas que discurren estrictamente sobre contenidos específicos, a sa- ber: 1. El parto y sus fases, 2. Pruebas de Bienestar Fetal, 3. Amenaza de Parto Pretérmino, 4. Ruptura Prematura de Membranas, 5. Amenaza de aborto, 6. Desprendimiento de placenta, 7. Infecciones de vías urinarias en embarazadas, 8. Diabetes Gestacional, 9. Hipertension en las embarazadas y 10. Preeclamp- sia y eclampsia En el primer tema, el Parto y sus fases, se precisan diferentes nociones sobre 26 GINECOLOGIA - OBSTETRICIA el proceso y el resultado de parir (dar a luz). A lo largo de la historia ha evolu- cionado el conocimiento de este tema dando como resultado una terminología precisa sobre los diferentes tipos de parto: parto natural, parto normal, parto ins- trumental, parto pretérmino, parto humanizado, etc. Estas nociones obedecen a determinadas circunstancias específicas que lo circunscribe como el uso o no de instrumentos que ayuden al nacimiento de un feto. De manera general, el parto marca el final del embarazo y el nacimiento de la criatura que se engendraba en el útero de la madre. Este proceso por el que la mujer o la hembra de una especie vivípara expulsa el feto y la placenta al final de la gestación consta de tres fases: la fase de dilatación, la de expulsión y la placentaria o de alumbramiento. En el segundo tema titulado Pruebas de Bienestar Fetal, se destaca el desa- rrollo de diferentes pruebas para el control del bienestar fetal. Éstas constitu- yen las técnicas aplicadas a las madres que permiten predecir el posible riesgo fetal o hacer un pronóstico del estado actual del feto, es decir, que tratan de conseguir a través de una valoración del feto de forma sistemática, la identifi- cación de aquellos que están en peligro dentro del útero materno, para así to- mar las medidas apropiadas y prevenir un daño irreversible. Se abordan en este contexto las indicaciones y los métodos (clínicos, biofísicos y bioquímicos más utilizados para el control de bienestar fetal. En el tema tres (3) denominado Amenaza de Parto Pretérmino, el trabajo se centra, en el desarrollo de los siguientes ítems. La Definición de Parto Pretérmi- no, la Definición de amenaza de Parto Pretérmino, la Evaluación del riesgo, la etiología, la Clínica de la Amenaza de Parto Pretérmino, el Diagnóstico precoz de la Amenaza de Parto Pretérmino, la Evaluación de gestantes que acuden a emergencia por signos y síntomas de Amenaza de Parto Pretérmino y el trata- miento. El trabajo parte de la definición de Parto Pretérmino entendido como aquel que ocurre después de la semana 23 y antes de la semana 37 de gestación, para posteriormente, tratar lo relativo a la Amenaza de Parto Pretérmino (APP) definido como el proceso clínico sintomático (Aparición de dinámica uterina regular acompañado de modificaciones cervicales) que puede conducir a un parto pretérmino. Su etiología es compleja y multifactorial, en la que pueden intervenir de forma simultánea factores inflamatorios, isquémicos, inmunológi- cos, mecánicos y hormonales. 27 GINECOLOGIA - OBSTETRICIA Por otro parte, el tema cuatro (4) expone la Ruptura Prematura de Membra- nas, la cual constituye una complicación usual en la práctica obstétrica, esta puede aumentar la incidencia en la morbilidad y mortalidad materna – fetal. Múltiples estudios se están llevando a cabo para poder dilucidar completamente su fisiopatología, lo cual se hace cada vez más necesario para poder aplicar estos conceptos en la práctica clínica, la evidencia actual indica que la Ruptura Prematura de Membrana es un proceso que puede ser afectado por factores: bioquímicos, fisiológicos, patológicos y ambientales. El capítulo cinco (5) comprende la temática sobre la Amenaza de aborto. (AA) que es la complicación más común durante el embarazo, se define como el sangrado transvaginal antes de las 20 semanas de gestación (SDG) gestación o con un feto menor de 500g, con o sin contracciones uterinas, sin dilatación cervical y sin expulsión de productos de la concepción”. Es decir, se presenta hemorragia de origen intrauterino antes de la vigésima semana completa de ges- tación, con o sin contracciones uterinas, sin dilatación cervical y sin expulsión de los productos de la concepción. Los síntomas abarcan amenorrea secundaria, presencia de vitalidad fetal y cólica abdominales con o sin sangrado vaginal entre otros. Para el diagnóstico se puede hacer una ecografía abdominal o va- ginal, examen pélvico y de laboratorio. En un principio el tratamiento consiste en recomendar reposo en cama y reposo pélvico. La identificación de factores de riesgo, el Ultrasonido obstétrico y la medición de marcadores bioquímicos son de gran importancia para realizar un diagnóstico y establecer un pronóstico oportuno. Estos aspectos y otros relacionados con el tema como son: la clínica, el protocolo a seguir, el tratamiento y la prevención, son tratados en este capí- tulo. El tema Desprendimiento de placenta es desarrollado a lo largo del tema seis (6). Su contenido aborda los aspectos importes como los factores de riesgo, etiología, síntomas y signos, diagnóstico y tratamiento de esta complicación cuyo proceso se caracteriza por el desprendimiento total o parcial, antes del parto, de una placenta que esta insertada en su sitio normal. Este hecho que puede traer grandes consecuencias para el feto y para la madre, puede ocurrir en cualquier momento del embarazo. Los desprendimientos producidos antes de las 20 semanas, por su evolución, deberán ser tratados como abortos. Los que tienen lugar después de la semana 20 de gestación y antes del alumbramiento constituyen el cuadro conocido como desprendimiento prematuro de la placenta normalmente insertada. (abrptio plantae o accidente de Baudelocque). El pro- ceso ha tenido una variedad de denominaciones a lo largo del tiempo y son consecuencia de la diversidad de cuadros clínicos que pueden producirse, sien- do las más empleadas en la actualidad: abruptio placentae, ablatio placentae, desprendimiento prematuro de placenta normalmente inserta (DPPNI), junto con el término abreviado desprendimiento prematuro de placenta (DPP). Para hablar de otra importante complicación que aqueja a la gestante y su bebe por nacer se expone en el tema (7) relacionado con las Infecciones de vías urinarias en embarazadas. Los particulares cambios morfológicos y funcio- nales que se producen en el tracto urinario de la gestante hacen que la infec- ción del tracto urinario (ITU) sea la segunda patología médica más frecuente del embarazo, por detrás de la anemia. Las 3 entidades de mayor repercusión son: Bacteriuria asintomática (BA) (2-11%), cuya detección y tratamiento son fundamentales durante la gestación, pues se asocia a prematuridad, bajo peso y elevado riesgo de progresión a pielonefritis aguda (PA) y sepsis; la Cistitis aguda (CA) (1,5%) y la Pielonefritis aguda (1-2%), principal causa de ingreso no obstétrico en la gestante, que en el 10 al 20% de los casos supone alguna complicación grave que pone en riesgo la vida materna y la fetal. La Diabetes Gestacional se ubica y desarrolla en el tema ocho (8). Este tipo de diabetes que aparece o se diagnostica durante el embarazo ha aumentado su prevalencia y cobrado gran relevancia epidemiológica en los últimos años. La Diabetes Gestacional (DG) o Diabetes Mellitius Gestacional (DMG) se carac- teriza por una secreción de insulina insuficiente para compensar la resistencia a la hormona, propia del embarazo. Después del parto, los niveles de glucosa sanguínea suelen normalizarse; sin embargo, algunas mujeres desarrollan DM tipo 2 y se asocia con complicaciones graves en la madre y el hijo, incluso años después del nacimiento. La Hipertensión en las Embarazadas, tema tan tratado y controvertido en los últimos años por su significación a nivel de que es la complicación médica 29 GINECOLOGIA - OBSTETRICIA más frecuente de la gestación y ocurre según estudios comprobados en el 7% a 10% de los embarazos y constituye una causa importante de morbimortalidad materna y perinatal. De manera clásica, la HTA en el embarazo ha sido definida como el incremento, durante la gestación, de la presión arterial sistólica (PAS) en 30 mmHg o más y/o la presión arterial diastólica (PAD) en 15 mmHg o más comparado con el promedio de valores previos a la 20va. semana de gestación. Cuando no se conocen valores previos, una lectura de 140/90 mmHg o mayor es considerada como anormal. El tema desarrollado abarca una visión general sobre algunos aspectos relativos a la definición y su clasificación, los factores predisponentes, sintomatología, diagnóstico, tratamiento, etc. Por último, el tema 10 aborda dos alteraciones íntimamente ligadas a la hi- pertensión arterial en el embarazo: la preeclampsia y la eclampsia. Éstas son en ocasiones tratadas como componentes de un mismo síndrome ya que la pree- clampsia es la hipertensión de reciente comienzo con proteinuria después de las 20 semanas de gestación y la eclampsia es la presencia de convulsiones genera- lizadas inexplicables en pacientes con preeclampsia.