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Project description:Preimplantation alcohol exposure can negatively impact embryonic development through disruption of molecular profiles and lead to fetal alcohol spectrum disorder (FASD). Despite the central role of the placenta in proper embryonic development and successful pregnancy, studies on the placenta in a FASD context are markedly lacking. Here, preimplantation binge-like alcohol exposure was implemented on pregnant C57BL/6 female mice through subcutaneous injection with two doses of either 2.5 g/kg 50% ethanol or an equivalent volume of saline at 2-h intervals on embryonic day 2.5 corresponding to the 8-cell stage. The placental morphology, DNA methylation and gene expression patterns in male and female late-gestation (E18.5) placentas were assessed. While overall placental morphology was not affected, we found a significant decrease in male ethanol-exposed embryo weights. When looking at molecular profiles, we uncovered numerous differentially methylated regions (DMRs ≥10% difference; 991 in males; 1309 in females) and differentially expressed genes (DEGs; 1046 in males; 340 in females) in the placentas. Remarkably, only 21 DMRs and 54 DEGs were common to both sexes, which were enriched for genes involved in growth factor response pathways. Preimplantation alcohol exposure had a greater impact on imprinted genes expression in male placentas (imprinted DEGs: 18 in males; 1 in females). Finally, by using L1-regularized linear regression, we were able to precisely discriminate control and ethanol-exposed placentas based on their specific DNA methylation patterns. This is the first study demonstrating that preimplantation alcohol exposure alters the DNA methylation and transcriptomic profiles of late-gestation placentas in a sex-specific manner. Importantly, it reveals a placental DNA methylation signature that can detect prenatal alcohol exposure in early life in order to provide appropriate support to attenuate and prevent eventual impact.
2024-02-07 | GSE254845 | GEO
Project description:Preimplantation alcohol exposure can negatively impact embryonic development through disruption of molecular profiles and lead to fetal alcohol spectrum disorder (FASD). Despite the central role of the placenta in proper embryonic development and successful pregnancy, studies on the placenta in a FASD context are markedly lacking. Here, preimplantation binge-like alcohol exposure was implemented on pregnant C57BL/6 female mice through subcutaneous injection with two doses of either 2.5 g/kg 50% ethanol or an equivalent volume of saline at 2-h intervals on embryonic day 2.5 corresponding to the 8-cell stage. The placental morphology, DNA methylation and gene expression patterns in male and female late-gestation (E18.5) placentas were assessed. While overall placental morphology was not affected, we found a significant decrease in male ethanol-exposed embryo weights. When looking at molecular profiles, we uncovered numerous differentially methylated regions (DMRs ≥10% difference; 991 in males; 1309 in females) and differentially expressed genes (DEGs; 1046 in males; 340 in females) in the placentas. Remarkably, only 21 DMRs and 54 DEGs were common to both sexes, which were enriched for genes involved in growth factor response pathways. Preimplantation alcohol exposure had a greater impact on imprinted genes expression in male placentas (imprinted DEGs: 18 in males; 1 in females). Finally, by using L1-regularized linear regression, we were able to precisely discriminate control and ethanol-exposed placentas based on their specific DNA methylation patterns. This is the first study demonstrating that preimplantation alcohol exposure alters the DNA methylation and transcriptomic profiles of late-gestation placentas in a sex-specific manner. Importantly, it reveals a placental DNA methylation signature that can detect prenatal alcohol exposure in early life in order to provide appropriate support to attenuate and prevent eventual impact.
2024-02-07 | GSE254846 | GEO
Project description: Not available
| S-EPMC8381495 | biostudies-literature
Project description:Prenatal alcohol exposure is recognized to alter DNA methylation profiles of brain cells during development, and as being part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol during the initial embryonic stages, a window marked with dynamic DNA methylation reprogramming, and on how this may rework the brain developmental program. Using a pre-clinical in vivo mouse model, we show that pre-implantation alcohol exposure leads to adverse developmental outcomes that replicate clinical facets observed in children with FASD. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinted control regions, and abnormal re-establishment of de novo DNA methylation profiles in various biological pathways (e.g, neural/brain development). These findings support the contribution of alcohol-induced DNA methylation programming deviations during pre-implantation to the manifestations of neurodevelopmental phenotypes associated with FASD.
2023-01-17 | GSE162765 | GEO
Project description: Not available
| S-EPMC3741219 | biostudies-literature
Project description: Not available
| S-EPMC6547370 | biostudies-literature
Project description: Not available
| S-EPMC8107644 | biostudies-literature
Project description: Not available
| S-EPMC6857007 | biostudies-literature
Project description: Not available
| S-EPMC8482819 | biostudies-literature
Project description:Transfer of frozen-thawed embryos leads to sex-specific DNA hypermethylation in both human and mouse placentas. : In humans, frozen ET led to placentas with significant alterations in DNA methylation with most genes demonstrating hypermethylation compared to placentas from fresh ET (4402 CpGs; 1600 genes; p-value < 0.05 in two–tailed unpaired t tests, and a mean methylation difference > 0.05). When compared to control samples, both frozen and fresh samples showed significant differences in methylation.(Frozen vs Control: 5600 CpGs, 2775 genes; Fresh vs Control: 4096 CpGS; 1914 genes; p-value < 0.05, mean methylation difference > 0.05). Paired analysis showed similar trends, despite controlling for maternal environment. Sex specific analysis revealed that these changes were primarily driven by male placentas, as seen by a larger number of CpGs that were differentially methylated, and a larger proportion of genes with at least 2 differentially methylated CpG sites in male placentas as compared to female placentas. (Males: 15572 CpGs, 4399 genes; Females: 7441 CpGs, 3070 genes; p-value < 0.05, mean methylation difference > 0.05). In order to isolate the effects of vitrification we utilized the mouse model, controlling for the effect of the maternal hormonal milieu. In the first genome-wide profiling of DNA methylation in a mouse IVF model, we found that trends in DNA methylation differences paralleled those seen in human placentas. Using similar significance cutoffs as for human samples, and BumpHunter analysis that identifies differentially methylated regions to compensate for a lower number of samples, placentas derived from frozen embryos were predominantly hypermethylated compared to placentas after fresh ET (589 DMRs, 445 genes). Both frozen and fresh embryo transfer samples demonstrated perturbations compared to control samples (Frozen vs Control: 1787 DMRs, 1319 genes; Fresh vs Control: 1119 DMRs, 808 genes). Consistent with the sex-specific trends we observed in human placentas, differences between samples derived from frozen compared to fresh embryo transfer were driven by changes in male placentas (Males: 1069 DMRs, 798 genes; Females:14 DMRs, 11 genes) . When considering the effect of IVF as a whole, murine placentas were predominantly hypomethylated, replicating existing human genome-wide methylation data. As seen previously, IVF led to changes in placental weight, placental morphology and microvessel density in mice, but no persistent changes were seen after embryo vitrification alone. Sexually dimorphic epigenetic changes could indicate differential susceptibility of male and female embryos to IVF-associated perturbations. This observation highlights the importance of sex-specific evaluation of the incidence of adverse outcomes. Similarities between changes seen in mouse and human samples underscore the suitability of the mouse model in evaluating the effect of ART on the epigenetic landscape. This convergence is especially valuable, given limited access to human tissues and the ability to isolate specific interventions in the mouse model.
2023-01-01 | GSE196547 | GEO