Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE179973 | GEO | 2021/07/15
REPOSITORIES: GEO
Similar Datasets
Project description:In this study, we describe the use of high-throughput sequencing to investigate the developmental basis of preimplantation embryos sired by alcohol-exposed males through in vitro fertilization (IVF). We exposed C57BL/6J male mice to one of three treatment groups. Sexually mature males were randomly selected to voluntarily consume 0% ethanol (control), 6% ethanol, or 10% ethanol for ten weeks. After treatment, the males were sacrificed for sperm collection and cryopreservation for IVF procedures. C57BL/6J donor females remained naïve to alcohol and were synchronized and superovulated before being sacrificed for oocyte collection. Oocytes underwent IVF with the cryopreserved semen and incubated until they reached the morula stage. The morulae sired by ethanol-exposed sperm exhibited altered transcriptional signatures compared to the control-sired morulae. Quick Biology Inc. sequencing core isolated total RNA from three pools (10-15 cells) of unsexed morulae from each control and ethanol preconception treatment. After obtaining the sequencing data, we conducted deep-sequencing analyses of the morulae transcriptomes. This experiment revealed sire alcohol consumption modifies preimplantation embryo genetic pathways controlling mitochondrial dysfunction and oxidative phosphorylation. This experiment furthers our understanding of growth and development changes induced by preconception paternal exposures.
2022-10-07 | GSE214726 | GEO
Project description:Using a mouse model, studies by our group reveal that paternal preconception alcohol intake affects offspring fetal-placental growth, with long-lasting consequences on adult metabolism. Here, we tested the hypothesis that chronic preconception male alcohol exposure impacts histone enrichment in sperm and that these changes are associated with altered developmental programming in the placenta. Using chromatin immunoprecipitation, we find alcohol-induced increases in sperm histone H3 lysine 4 trimethylation (H3K4me3) that map to promoters and presumptive enhancer regions enriched in genes driving neurogenesis and craniofacial development. Given the colocalization of H3K4me3 with the chromatin binding factor CTCF across both sperm and embryos, we next examined CTCF localization in the placenta. We find global changes in CTCF binding within placentae derived from the male offspring of alcohol-exposed sires. Furthermore, altered CTCF localization correlates with dysregulated gene expression across multiple gene clusters; however, these transcriptional changes only occur in male offspring. Finally, we identified a correlation between genomic regions exhibiting alcohol-induced increases in sperm H3K4me3 and increased CTCF binding in male placentae. Collectively, our analysis demonstrates that the chromatin landscape of sperm is sensitive to chronic alcohol exposure and that a subset of these affected regions exhibits increased placental CTCF enrichment.
2022-05-24 | GSE203189 | GEO
Project description:Using an established mouse model of chronic exposure, previous work by our group had linked preconception paternal alcohol use to sex-specific patterns of fetal growth restriction and placental dysfunction. The goal of the present study was to investigate the long-term impact chronic preconception paternal alcohol exposure has on offspring growth and metabolic programming. In the male offspring, we observed increases in both the expression of genes within the pro-fibrotic TGF-ß signaling pathway as well as total levels of cellular hydroxyproline within the liver. Further, we identified suppressed cytokine profiles, which could be linked to the up-regulation of genes in the LiverX/RetinoidX/FarnesoidX Receptor pathways.
2018-07-24 | GSE117559 | GEO
Project description:<p>The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is not explored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birthweight, severe growth restriction, and premature mortality. Paternal transmission of disease risk is provoked by pervasive microbiome perturbations, including (non)-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the gut microbiota prior to conception. This reflects a dynamic male reproductive response to induced dysbiosis, that includes impaired leptin signalling, an altered metabolite and physiological configuration in testes, and remapped small RNA payloads in sperm. As a result, dysbiotic males trigger in utero placental insufficiency, which exhibits hallmarks of pre-eclampsia, and reveals a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, that is sensitive to environmental exposures, and programs offspring fitness through impacting placental function. </p>
2024-02-12 | MTBLS1629 | MetaboLights
Project description:one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine (Hcy) levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. We determined that betaine-homocysteine S-methyltransferase 1 (BHMT1), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p<0.05).
2015-09-07 | PXD002578 | Pride
Project description:Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health and development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites in males were associated with altered sperm methylation and blastocyst-stage embryo development. To corroborate this, we examined the effect of preconception exposure to di(2-ethylhexyl) phthalate (DEHP) on genome-wide DNA methylation and gene expression profiles in mice. We found that male preconception DEHP exposure resulted in 704 differentially methylated regions (DMRs; q-value < 0.05; ³ 10% methylation change) in sperm, 1,716 DMRs in embryonic, and 3,181 DMRs in extra-embryonic tissue. Of these, 29 DMRs overlapped between sperm and F1 tissues, half of which showed concordant methylation changes between F0 and F1 generations. F1 transcriptomes at E7.5 were also altered by male preconception DEHP exposure including developmental gene families such as Hox, Gata, and Sox. Additionally, gene ontology analyses of DMRs and differentially expressed genes showed enrichment of multiple developmental processes including embryonic development, pattern specification and morphogenesis.
2022-02-28 | GSE174093 | GEO
Project description:Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males
| PRJNA745997 | ENA
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: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:Growth restriction, craniofacial dysmorphology and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal and/or postnatal, but the underlying mechanisms remain unknown. We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome, e.g. craniofacial changes and growth restriction in adolescent mice. Here we further characterize the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of non-fostered ethanol-exposed and control mice at postnatal day 28. We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiological result of ethanol exposure in utero. We also find that, despite some catch-up growth after five weeks of age, the effect extends into adulthood, consistent with longitudinal studies in humans. Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis and lipid metabolism. Gene expression changes in the livers of offspring exposed to alcohol in utero compared to controls.
2010-09-30 | E-GEOD-23106 | biostudies-arrayexpress