Fetus

About: Fetus is a research topic. Over the lifetime, 21567 publications have been published within this topic receiving 646380 citations. The topic is also known as: foetus & fœtus.

Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome

Abstract: Chromatin structure is epigenetically altered via covalent modifications of histones to allow for heritable gene regulation without altering the nucleotide sequence. Multiple lines of evidence from rodents have established a role for epigenetic remodeling in regulating gene transcription in response to an altered gestational milieu. However, to date, it is unknown whether variations in the intrauterine environment in primates similarly induce changes in key determinants of hepatic chromatin structure. We hypothesized that a maternal high-fat diet would alter the epigenomic profile of the developing offspring, which would result in alterations in fetal gene expression. Age- and weight-matched adult female Japanese macaques were placed on control (13% fat) or high-fat (35% fat) breeder diets and mated annually over a 4-year interval. Fetuses in successive years were delivered near term (e130 of 167 days) and underwent necropsy with tissue harvest. Fetal histones were acid extracted for characterization of H3 modification and chromatin immunoprecipitation (ChIP) with differential display PCR; fetal RNA, DNA, and cytoplasmic and nuclear protein extracts were similarly extracted for comparison. Chronic consumption of a maternal high-fat diet results in a threefold increase in fetal liver triglycerides and histologic correlates of non-alcoholic fatty liver disease. These gross changes in the fetal liver are accompanied by a statistically significant hyperacetylation of fetal hepatic tissue at H3K14 (199.85+/-9.64 vs 88.8+/-45.4; P=0.038) with a trend towards the increased acetylation at H3K9 (140.9+/-38.7 vs 46.6+/-6.53; P=0.097) and at H3K18 (69.0+/-3.54 vs 58.0+/-4.04; P=0.096). However, epigenetic modifications on fetal hepatic H3 associated with gene repression were absent or subtle (P>0.05). Subsequent characterization of key epigenetic determinants associated with H3 acetylation marks revealed similar significant alterations in association with a high-fat maternal diet (e.g., relative fetal histone deacetylase 1 (HDAC1) gene expression 0.61+/-0.25; P=0.011). Consistent with our mRNA expression profile, fetal nuclear extracts from offspring of high-fat diet animals were observed to be significantly relatively deplete of HDAC1 protein (36.07+/-6.73 vs 83.18+/-7.51; P=0.006) and in vitro HDAC functional activity (0.252+/-0.03 vs 0.698+/-0.02; P<0.001). We employ these observations in ChIP differential display PCR to attempt to identify potential fetal genes whose expression is reprogramed under conditions of a high-fat maternal diet. We quantitatively confirm a minimum of a 40% alteration in the expression of several genes of interest: glutamic pyruvate transaminase (alanine aminotransferase) 2 (GPT2) (1.59+/-0.23-fold; P=0.08), DNAJA2 (1.36+/-0.21; P=0.09), and Rdh12 (1.88+/-0.15; P=0.01) are appreciably increased in fetal hepatic tissue from maternal caloric-dense diet animals when compared with control while Npas2, a peripheral circadian regulator, was significantly downmodulated in the offspring of high-fat diet animals (0.66+/-0.08; P=0.03). In this study, we show that a current significant in utero exposure (caloric-dense high-fat maternal diet) induces site-specific alterations in fetal hepatic H3 acetylation. Employing ChIP, we extend these observations to link modifications of H3 acetylation with alterations in gene-specific expression. These results suggest that a caloric-dense maternal diet leading to obesity epigenetically alters fetal chromatin structure in primates via covalent modifications of histones and hence lends a molecular basis to the fetal origins of adult disease hypothesis.

Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth.

Abstract: To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus

Abstract: Objective To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses Methods This was a prospective observational study in a tertiary care/teaching hospital Twenty-six women who were diagnosed with growth-restricted fetuses by local standards before 32 weeks' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study To compare Doppler changes as a function of time, pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements Biometry for assessment of fetal growth was performed every 2 weeks Computerized fetal heart rates were obtained daily Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded Perinatal outcome endpoints included: intrauterine death, gestational age at delivery, newborn weight, central nervous system damage of grade 2 or greater, intraventricular hemorrhage and neonatal mortality Results Mean gestational age and newborn weight at delivery were 29 (standard deviation (SD), 2) weeks and 818 (SD, 150) g, respectively The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events First, for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality Second, severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into ‘early’ and ‘late’ Doppler changes Early changes occurred in peripheral vessels (umbilical and middle cerebral arteries; 50% of patients affected 15–16 days prior to delivery) Late changes included umbilical artery reverse flow, and abnormal changes in the ductus venosus, aortic and pulmonary outflow tracts (50% of patients affected 4–5 days prior to delivery) The time interval between the occurrence of early and late changes was significantly different (P < 00001) and late changes were significantly associated with perinatal death (P < 001) Conclusions Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death Copyright © 2002 ISUOG

Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome

Abstract: Objective: To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6). Methods: The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM. Results: The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm l...