Project description:Neural-tube defects (NTDs) are common birth defects of complex etiology. Although many studies have confirmed a genetic component, the exact mechanism between DNA methylation and NTDs remains unclear.In this study,the alteration of methylation from placental tissues of normal infants or with NTDs.Results demonstrated that DNA methylation changed in specific gene location.
Project description:<p>Maternal folic acid intake is crucial for the development of the offspring's nervous system, and folic acid metabolism disorders during pregnancy lead to neural tube defects (NTDs) in the fetus. Folic acid and vitamins biosynthesis is a major biochemical feature of gut microbiota. The complex and diverse microbial ecosystem residing within maternal host contributes critically to these intergenerational impacts. However, the mechanisms still require further investigation. In this study, we found that the low folate diets combined MTX-induced changed the structure/composition of the gut microbiota and substantially altered the fecal metabolic phenotype of pregnant mice, including central carbon metabolism in cancer and vitamin digestion & absorption. We demonstrated that the correlation betweent gut microbiota of pregnant mice and the brain metabolic profiles of NTDs fetal mice. According to our data, the Lactobacillales and Bifidobacteriales abundances in pregnant mice gut were positively correlated with the abundances of lipid metabolites in fetal mice brain. The abundances of Enterobacterales and Clostridiales were negatively correlated with those lipid metabolites. Interestingly, the abundance of Inosine, Uridine, L-Carnitine and Glycerophosphocholine were down-regulated synchronously in pregnant feces and NTDs fetal mice brain. This was probably the intergenerational microbial-metabolism biomarkers of NTDs. Our study provides evidence for how perinatal microecological factors shape fetal neural tube development.</p><p><br></p><p><strong>Feces metabolomics</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4893' rel='noopener noreferrer' target='_blank'><strong>MTBLS4893</strong></a>.</p><p><strong>Brain tissue metabolomics</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4894' rel='noopener noreferrer' target='_blank'><strong>MTBLS4894</strong></a>.</p>
Project description:Exposure to ionizing radiation around the time of neural tube closure results in a number of developmental defects, including neural tube defects (e.g. exencephaly, cleft palate) and eye defects (e.g. microphtalmos, anaphtalmos). These defects result from perturbed neural tube closure and development of the presumptive eye. In order to better understand the underlying molecular mechanisms, gene expression profiling was performed in heads of mouse embryos at embryonic day 9, after they had been irradiated at embryonic day 7.5 with 1 Gy of X-rays. Non-irradiated mice served as controls for differential gene expression.
Project description:Background: A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome. Methods: We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing. Results: Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET) although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age. Conclusion: Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary. Bisulphite converted DNA from the 48 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:Genome wide DNA methylation profiling of human fetal retina samples. The Illumina Infinium DNA methylation Beadchip was used to obtain DNA methylation profiles in human fetal retina samples that were cultured in different ways. To better undrestand the relationship between developmental stage and epigenetic age (measured by the Horvath clock based on 353 CpGs as detailed in pubmed identifier: 24138928), we analyzed the highly regular sequence of developmental stage in the human neural retina. Findings: epigenetic age of fetal retina is highly correlated with chronological age. We find that epigenetic aging progresses normally in vitro. The correlation is retained in stem cell derived organoids but is accelerated in individuals with Down syndrome.
Project description:Genome wide DNA methylation profiling of human fetal retina samples. The Illumina Infinium DNA methylation Beadchip was used to obtain DNA methylation profiles in human fetal retina samples that were cultured in different ways. To better undrestand the relationship between developmental stage and epigenetic age (measured by the Horvath clock based on 353 CpGs as detailed in pubmed identifier: 24138928), we analyzed the highly regular sequence of developmental stage in the human neural retina. Findings: epigenetic age of fetal retina is highly correlated with chronological age. We find that epigenetic aging progresses normally in vitro. The correlation is retained in stem cell derived organoids but is accelerated in individuals with Down syndrome.
Project description:This study aims to identify genome-wide placental DNA differential methylation positions (DMPs) in fetal overgrowth and the associations with fetal growth factors, leptin and adiponectin. In the Shanghai Birth Cohort, we studied 30 pairs of placentals of large-for-gestational-age (LGA, birth weight>90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25th-75th percentiles, control) newborns matched by sex and gestational age. Placental DNA methylations were measured by the Illumina Infinium Human Methylation-EPIC BeadChip. Cord blood insulin, C-peptide, proinsulin, IGF-1, IGF-2, leptin and adiponectin concentrations were measured. We identified 543 DMPs (397 hypermethylated, 146 hypomethylated) comparing LGA vs. OGA at false discovery rate <5% and absolute methylation difference >0.05 adjusting for placental cell type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. We validated a hyper-methylated gene - cadherin 13 (CDH13) reported in a previous epigenome-wide association study, and validated a newly discovered differentially (hyper-)methylated gene -visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (47 LGA-control pairs). Pathway analysis did not detect any statistically significant pathway correcting for multiple tests. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while other observed biomarkers were not. Fetal overgrowth was associated with a large number of altered placental gene DNA methylations. The study provides robust evidence suggesting that placental CDH13 and VSX1 genes are hyper-methylated in LGA. Placental gene methylation was correlated with cord blood biomarker for adiponectin, but not for leptin and fetal growth factors.
Project description:To assess the impact of postnatal processing on placental DNA methylation, array data from flash frozen placental tissue was compared to perfluorocarbon-immersed and formalin fixed paraffin embedded placental tissue. We observed tissue exposed to perfluorocarbon showed no significant DNA methylation differences when compared to unprocessed tissue, while formalin processing altered the quality and reliability of the data produced on the DNA methylation array platform. Placental DNA methylation allows for the study of gene-environment interactions that influence the fetal environment and development. Our study highlights that placental postprocessing techniques must be considered in the evaluation and interpretation of epigenetic studies.
Project description:Genome wide DNA methylation profiling of normal and pathological placental villous tissue samples. The Illumina EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles.