Maternal Vitamin and Mineral Supplementation and Rate of Maternal Weight Gain Affects Placental Expression of Energy Metabolism and Transport-Related Genes.
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ABSTRACT:
SUBMITTER: Diniz WJS
PROVIDER: S-EPMC8001966 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vitamin D deficiency is a highly prevalent obstetrical concern associated with an increased risk of complications like pre-eclampsia, gestational diabetes, and growth retardation. Vitamin D status in pregnancy is also linked to long-term offspring health, e.g., the risk of obesity, metabolic disease, and neurodevelopmental problems. Despite the suspected role of vitamin D in placental diseases and fetal development, there is limited knowledge on the effect of vitamin D on placental function. Thus, we performed next-generation RNA sequencing, comparing the placental transcriptome from uncomplicated term pregnancies receiving the often-recommended dose of 10 µg vitamin D/day (n = 36) with pregnancies receiving 90 µg/day (n = 34) from late first trimester to delivery. Maternal vitamin D status in the first trimester was also considered. We found that signaling pathways related to cell adhesion, immune function, and neurodevelopment were affected, supporting that increased vitamin D supplementation benefits placental function in established pregnancies without severe vitamin D deficiency, also underlining the importance of vitamin D in brain development. Specific effects of the first trimester vitamin D status and offspring sex were also identified. Further studies are warranted, addressing the optimal vitamin status during pregnancy with a focus on organ-specific vitamin D needs in individual pregnancies.
| S-EPMC10745524 | biostudies-literature
Project description:BackgroundMaternal obesity prior to or during pregnancy influences fetal growth, predisposing the offspring to increased risk for obesity across the life course. Placental epigenetic mechanisms may underlie these associations. We conducted an epigenome-wide association study to identify placental DNA methylation changes associated with maternal prepregnancy body mass index (BMI) and rate of gestational weight gain at first (GWG1), second (GWG2), and third trimester (GWG3).MethodParticipants of the NICHD Fetal Growth Studies with genome-wide placental DNA methylation (n = 301) and gene expression (n = 75) data were included. Multivariable-adjusted regression models were used to test the associations of 1 kg/m2 increase in prepregnancy BMI or 1 kg/week increase in GWG with DNA methylation levels. Genes harboring top differentially methylated CpGs (FDR P < 0.05) were evaluated for placental gene expression. We assessed whether DNA methylation sites known to be associated with BMI in child or adult tissues, were also associated with maternal prepregnancy BMI in placenta.ResultsPrepregnancy BMI was associated with DNA methylation at cg14568196[EGFL7], cg15339142[VETZ], and cg02301019[AC092377.1] (FDR P < 0.05, P ranging from 1.4 × 10-10 to 1.7 × 10-9). GWG1 or GWG2 was associated with DNA methylation at cg17918270[MYT1L], cg20735365[DLX5], and cg17451688[SLC35F3] (FDR P < 0.05, P ranging from 6.4 × 10-10 to 1.2 × 10-8). Both prepregnancy BMI and DNA methylation at cg1456819 [EGFL7] were negatively correlated with EGFL7 expression in placenta (P < 0.05). Several CpGs previously implicated in obesity traits in children and adults were associated with prepregnancy BMI in placenta. Functional annotations revealed that EGFL7 is highly expressed in placenta and the differentially methylated CpG sites near EGFL7 and VEZT were cis-meQTL targets in blood.ConclusionsWe identified placental DNA methylation changes at novel loci associated with prepregnancy BMI and GWG. The overlap between CpGs associated with obesity traits in placenta and other tissues in children and adults suggests that epigenetic mechanisms in placenta may give insights to early origins of obesity.
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Project description: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.
| S-EPMC6698749 | biostudies-literature
Project description:Background: Fetal growth is dependent on placental nutrient supply, which is influenced by placental perfusion and transporter abundance. Previous research indicates that adequate choline nutrition during pregnancy improves placental vascular development, supporting the hypothesis that choline may affect placental nutrient transport.Objective: The present study sought to determine the impact of maternal choline supplementation (MCS) on placental nutrient transporter abundance and nutrient metabolism during late gestation.Methods: Female non-Swiss albino mice were randomly assigned to the 1×, 2×, or 4× choline diet (1.4, 2.8, and 5.6 g choline chloride/kg diet, respectively) 5 d before mating (n = 16 dams/group). The placentas and fetuses were harvested on gestational day (E) 15.5 and E18.5. The placental abundance of macronutrient, choline, and acetylcholine transporters and glycogen metabolic enzymes, and the placental concentration of glycogen were quantified. Choline metabolites and docosahexaenoic acid (DHA) concentrations were measured in the placentas and/or fetal brains. Data were stratified by gestational day and fetal sex and were analyzed by using mixed linear models.Results: At E15.5, MCS downregulated the placental transcript and protein abundance of glucose transporter 1 (GLUT1) (-40% to -73%, P < 0.05) and the placental transcript abundance of glycogen-synthesizing enzymes (-24% to -50%, P ≤ 0.05). At E18.5, MCS upregulated GLUT3 protein abundance (+55%, P = 0.016) and the transcript abundance of glycogen-synthesizing enzymes only in the female placentas (+36% to +60%, P < 0.05), resulting in a doubling (P = 0.01) of the glycogen concentration. A higher placental transcript abundance of the transporters for DHA, choline, and acetylcholine was also detected in response to MCS, consequently altering their concentrations in the placentas or fetal brains (P ≤ 0.05).Conclusions: These data suggest that MCS modulates placental nutrient transporter abundance and nutrient metabolism in late gestation of mouse pregnancy, with subsequent effects on nutrient supply for the developing fetus.
| S-EPMC10101224 | biostudies-literature
Project description:High temperature requirement factor A3 (HtrA3), a member of the HtrA protease family, is highly expressed in the developing placenta, including the maternal decidual cells in both mice and humans. In this study we deleted the HtrA3 gene in the mouse and crossed females carrying zero, one, or two HtrA3-expressing alleles with HtrA3+/- males to investigate the role of maternal vs fetal HtrA3 in placentation. Although HtrA3-/- mice were phenotypically normal and fertile, HtrA3 deletion in the mother resulted in intra-uterine growth restriction (IUGR). Disorganization of labyrinthine fetal capillaries was the major placental defect when HtrA3 was absent. The IUGR caused by maternal HtrA3 deletion, albeit being mild, significantly altered offspring growth trajectory long after birth. By 8 months of age, mice born to HtrA3-deficient mothers, independent of their own genotype, were significantly heavier and contained a larger mass of white fat. We further demonstrated that in women serum levels of HtrA3 during early pregnancy were significantly lower in IUGR pregnancies, establishing an association between lower HtrA3 levels and placental insufficiency in the human. This study thus revealed the importance of maternal HtrA3 in optimizing placental development and its long-term impact on the offspring well beyond in utero growth.
| S-EPMC5496872 | biostudies-other
Project description:The mammalian placenta is a source of endocrine signals that prime the onset of maternal care at parturition. While consequences of placental dysfunction for offspring growth are well defined, how altered placental signalling might affect maternal behaviour is unstudied in a natural system. In the cross between sympatric mouse species, Mus musculus domesticus and Mus spretus, hybrid placentas are undersized and show misexpression of genes critical to placental endocrine function. Using this cross, we quantified the effects of placental dysregulation on maternal and anxiety-like behaviours in mice that differed only in pregnancy type. Relative to mothers of conspecific litters, females exposed to hybrid placentas did not differ in anxiety-like behaviours but were slower to retrieve 1-day-old pups and spent less time in the nest on the night following parturition. Early deficits in maternal responsiveness were not explained by reduced ultrasonic vocalization production in hybrid pups and there was no effect of pup genotype on measures of maternal behaviour and physiology collected after the first 24 h postpartum. These results suggest that placental dysregulation leads to poor maternal priming, the effect of which is alleviated by continued exposure to pups. This study provides new insight into the placental mediation of mother-offspring interactions.
| S-EPMC6774950 | biostudies-literature
Project description:This experiment was conducted to investigate the effects of maternal catalase (CAT) supplementation on reproductive performance, antioxidant enzyme activities, mineral transport, and mRNA expression of related genes in sows and offspring. A total of 40 pregnant sows at 95 days of gestation with similar parity (3−5 parities) and back-fat thickness were assigned randomly and equally into the control (CON) group (fed a basal diet) and CAT group (fed a basal diet supplemented with 660 mg/kg CAT; CAT activity, 280 U/g). The reproductive performance was recorded, and the placenta and blood samples of sows and neonatal piglets, as well as the jejunum and ileum samples from neonatal boars (eight replicates per group), were collected. Results showed that dietary supplementation with CAT significantly decreased the intrauterine growth restriction (IUGR) rate and increased the activity of serum CAT in neonatal piglets and umbilical cords (p < 0.05). In addition, CAT supplementation tended to improve total antioxidant capacity (T-AOC) levels in the maternal serum (p = 0.089) and umbilical cords of piglets (p = 0.051). The serum calcium (Ca), manganese (Mn), and zinc (Zn) of farrowing sows and Mn concentration in the umbilical cord, and serum Ca, magnesium (Mg), copper (Cu), and Mn of neonatal piglets were significantly increased (p < 0.05) in the CAT group. CAT supplementation downregulated mRNA expression of TRPV6 and CTR1 (p < 0.05), Cu/Zn SOD (p = 0.086) in the placenta and tended to increase the mRNA expression of the glutathione peroxidase 1 (GPX1) (p = 0.084), glutathione peroxidase 4 (GPX4) (p = 0.063), and CAT (p = 0.052) genes in the ileum of piglets. These results showed that the maternal CAT supplementation improved fetal growth by decreasing the IUGR rate, and modulated antioxidant activity, as well as mineral elements in the pregnant sows and their piglets.
| S-EPMC8996845 | biostudies-literature
Project description:Introduction:Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as asthma. Sources of data:Synthesis of systematic and narrative reviews. Areas of agreement and controversy:The findings are generally inconsistent in most areas, and, at present, there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. In most areas, the evidence tends towards maternal vitamin D being of overall benefit, but often does not reach statistical significance in meta-analyses. Growing points and areas timely for developing research:The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily. High-quality randomized placebo-controlled trials, such as the UK-based MAVIDOS trial, will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes.
| S-EPMC6003599 | biostudies-literature
Project description:Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.
| S-EPMC4498463 | biostudies-literature
Project description:BackgroundMaternal metabolic abnormalities have been related to offspring obesity especially during childhood.ObjectivesWe analyzed whether the gestational diabetes mellitus (GDM)-associated melatonin receptor 1B (MTNR1B) genotype of mothers modified the relation between maternal gestational weight gain and childhood obesity.MethodsA total of 1114 Chinese mother-child pairs (mothers with or without prior GDM) were included. Mothers' MTNR1B rs10830962 genotype and gestational weight gain were assessed. Indicators of childhood obesity included BMI-for-age z-score, weight-for-age z-score, waist circumference, and body fat. Childhood overweight and obesity were also analyzed.ResultsWe found that the maternal MTNR1B genotype significantly interacted with gestational weight gain on indicators of offspring's obesity (all P for interaction < 0.05). After multivariable adjustment, BMI-for-age z-scores associated with 1-kg gestational weight gain were 0.009 (SE 0.018), 0.026 (SE 0.010), and 0.061 (SE 0.010) in children with the maternal MTNR1B genotype CC, CG, and GG, respectively (P-interaction = 0.012). Similar interactions were observed for weight-for-age z-score, waist circumference, and body fat (P-interaction = 0.001, 0.003, and 0.012, respectively). The associations remained consistently significant in women with and without GDM. We also found significant interactions between the maternal MTNR1B genotype and gestational weight gain on the offspring's childhood overweight and obesity (P-interaction = 0.005 and 0.026, respectively).ConclusionsThe maternal MTNR1B genotype might interact with gestational weight gain on offspring's obesity risk during childhood.
| S-EPMC6997086 | biostudies-literature