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Project description:Background : The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. The placenta forms mainly from fetal tissue and therefore has the same biological sex as the fetus it supports. Extensive research has delved into the placenta’s involvement in pregnancy complications and future offspring development, with a notable emphasis on exploring sex-specific disparities. However, despite these investigations, sex-based disparities in epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown. Methods : We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex differences in transcription and DNA methylation. Results Our comparison between male and female revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several DEGs were correlated with DMRs. A subset of the DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas (n = 348 DMRs on X chromosome and 19 DMRs on autosomes), while others were acquired later in placental development. Conclusion : Our study provides comprehensive lists of DEGs and DMRs between male and female that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
2023-12-31 | GSE252282 | GEO
Project description:Background: The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. Contrary to popular belief, the placenta forms mainly from fetal tissue; therefore, it has the same biological sex as the fetus it supports. However, while placental function is linked to increased risks of pregnancy complications and neurodevelopmental diseases in male offspring in particular, the sex-specific epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown.Methods: We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex-specific differences in transcription and DNA methylation. Results: Our sex-specific analysis revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Sex-specific differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several sex-specific DEGs were correlated with sex-specific DMRs. A subset of the sex-specific DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas, while others were acquired later in placental development.Conclusion: Our study provides comprehensive lists of sex-specific DEGs and DMRs that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
2023-12-30 | GSE252283 | GEO
Project description:Background: The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. Contrary to popular belief, the placenta forms mainly from fetal tissue; therefore, it has the same biological sex as the fetus it supports. However, while placental function is linked to increased risks of pregnancy complications and neurodevelopmental diseases in male offspring in particular, the sex-specific epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown.Methods: We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex-specific differences in transcription and DNA methylation. Results: Our sex-specific analysis revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Sex-specific differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several sex-specific DEGs were correlated with sex-specific DMRs. A subset of the sex-specific DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas, while others were acquired later in placental development.Conclusion: Our study provides comprehensive lists of sex-specific DEGs and DMRs that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
2023-12-30 | GSE252281 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-07 | GSE254847 | GEO
Project description:BackgroundsOne of the limitations of somatic cell nuclear transfer (SCNT) strategy to generate genetically modified offspring is the low birth rate. Placental dysfunction is one of the causes of abortion. Circular RNA (circRNA) is noncoding RNA which functions as microRNA (miRNA) sponges in biological processes.MethodsTwo aberrant pregnant placenta (aberrant group, AG) and three normal pregnant placenta (normal group, NG) during late gestation (180-210 days) with bovine SCNT fetus were collected for high-throughput sequencing and analyzed. The host genes of differentially expressed (DE) circRNAs were predicted. And the microRNAs (miRNAs) which could interact with DE circRNAs were analyzed. Then, the expressional level of partial DE circRNAs and corresponding host genes was verified through qRT-PCR. At last, the function of host genes was analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).ResultsAltogether 123 differentially expressed circRNAs between two groups were identified, which were found related to 60 host genes and 32 miRNAs. The top 10 upregulated circRNAs were bta_circ_0012985, bta_circ_0013071, bta_circ_0013074, bta_circ_0016024, bta_circ_0013068, bta_circ_0008816, bta_circ_0012982, bta_circ_0013072, bta_circ_0019285, and bta_circ_0013067. The top 10 downregulated circRNAs were bta_circ_0024234, bta_circ_0017528, bta_circ_0008077, bta_circ_0003222, bta_circ_0007500, bta_circ_0020328, bta_circ_0011001, bta_circ_0016364, bta_circ_0008839, and bta_circ_0016049. The qRT-PCR results showed consistent trend with sequencing analysis result, while host genes had no statistic difference. The GO and KEGG analyses of the host genes suggested that abnormal circRNA expression may play multiple roles in placental structure and dysfunction.ConclusionThe abnormal circRNA expression may be one of reasons of placental dysfunction, leads to abortion of bovine SCNT fetus.
| S-EPMC6642297 | biostudies-literature
Project description:PurposeTo determine the expression patterns of imprinted genes and their methylation status in aborted cloned porcine fetuses and placentas.MethodsRNA and DNA were prepared from fetuses and placentas that were produced by SCNT and controls from artificial insemination. The expression of 18 imprinted genes was determined by quantitative real-time PCR (q-PCR). Bisulfite sequencing PCR (BSP) was conducted to determine the methylation status of PRE-1 short interspersed repetitive element (SINE), satellite DNA and H19 differentially methylated region 3 (DMR3).ResultsThe weight, imprinted gene expression and genome-wide DNA methylation patterns were compared between the mid-gestation aborted and normal control samples. The results showed hypermethylation of PRE-1 and satellite sequences, the aberrant expression of imprinted genes, and the hypomethylation of H19 DMR3 occurred in mid-gestation aborted fetuses and placentas.ConclusionsCloned pigs generated by somatic cell nuclear transfer (SCNT) showed a greater ratio of early abortion during mid-gestation than did normal controls because of the incomplete epigenetic reprogramming of the donor cells. Altered expression of imprinted genes and the hypermethylation profile of the repetitive regions (PRE-1 and satellite DNA) may be associated with defective development and early abortion of cloned pigs, emphasizing the importance of epigenetics during pregnancy and implications thereof for patient-specific embryonic stem cells for human therapeutic cloning and improvement of human assisted reproduction.
| S-EPMC4389936 | biostudies-literature
Project description:BACKGROUND:DNA methylation is an important epigenetic modification that is essential for epigenetic gene regulation in development and disease. To date, the genome-wide DNA methylation maps of many organisms have been reported, but the methylation pattern of cattle remains unknown. RESULTS:We showed the genome-wide DNA methylation map in placental tissues using methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq). In cattle, the methylation levels in the gene body are relatively high, whereas the promoter remains hypomethylated. We obtained thousands of highly methylated regions (HMRs), methylated CpG islands, and methylated genes from bovine placenta. DNA methylation levels around the transcription start sites of genes are negatively correlated with the gene expression level. However, the relationship between gene-body DNA methylation and gene expression is non-monotonic. Moderately expressed genes generally have the highest levels of gene-body DNA methylation, whereas the highly, and lowly expressed genes, as well as silent genes, show moderate DNA methylation levels. Genes with the highest expression show the lowest DNA methylation levels. CONCLUSIONS:We have generated the genome-wide mapping of DNA methylation in cattle for the first time, and our results can be used for future studies on epigenetic gene regulation in cattle. This study contributes to the knowledge on epigenetics in cattle.
| S-EPMC3893433 | 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
Project description:BackgroundSex is an important covariate of epigenome-wide association studies due to its strong influence on DNA methylation patterns across numerous genomic positions. Nevertheless, many samples on the Gene Expression Omnibus (GEO) frequently lack a sex annotation or are incorrectly labelled. Considering the influence that sex imposes on DNA methylation patterns, it is necessary to ensure that methods for filtering poor samples and checking of sex assignment are accurate and widely applicable.ResultsHere we presented a novel method to predict sex using only DNA methylation beta values, which can be readily applied to almost all DNA methylation datasets of different formats (raw IDATs or text files with only signal intensities) uploaded to GEO. We identified 4345 significantly (p<0.01) sex-associated CpG sites present on both 450K and EPIC arrays, and constructed a sex classifier based on the two first principal components of the DNA methylation data of sex-associated probes mapped on sex chromosomes. The proposed method is constructed using whole blood samples and exhibits good performance across a wide range of tissues. We further demonstrated that our method can be used to identify samples with sex chromosome aneuploidy, this function is validated by five Turner syndrome cases and one Klinefelter syndrome case.ConclusionsThis proposed sex classifier not only can be used for sex predictions but also applied to identify samples with sex chromosome aneuploidy, and it is freely and easily accessible by calling the 'estimateSex' function from the newest wateRmelon Bioconductor package ( https://github.com/schalkwyk/wateRmelon ).
| S-EPMC8240370 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-06 | GSE168512 | GEO