Project description:Peripheral whole blood DNA methylation profiles of pregnant women with normal pregnancy from the 10th-14th weeks of gestation (average at the 10th week), 24th-28th weeks of gestation (average at the 25th week), 38th-40th weeks of gestation (average at the 38th week) and after delivery status (average at the 10th month after delivery)
Project description:Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. We characterized several models in which biological age, assessed primarily through analysis of DNA methylation, undergoes reversible changes. Pregnancy is one such example.
Project description:Genome wide DNA methylation analysis of 36 pregnant women during pregnancy. DNA methylation was investigated in maternal blood at two time points (1st and 3rd trimester) and in cord blood at birth using the Illumina EPIC array.
Project description:Co-ordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A non-receptive uterine environment may be a key contributor to pregnancy loss, as the majority of pregnancy losses occur prior to embryo implantation. DNA methylation has been highlighted as a potential contributor in regulating early pregnancy events in the uterus. It was hypothesized that DNA methylation regulates expression of key genes in the uterus during pregnancy. To gain support for this hypothesis the correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and sub-fertile dairy cow strains were obtained at day 17 of pregnancy or the reproductive cycle. Microarrays were used to characterize genome-wide DNA methylation profiles and data compared with transcription profiles which have been previously reported. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. The 1,000 most significant correlations were used for subsequent analysis. Of these, 52% percent were negatively correlated with gene expression. When this gene list was compared with previously reported gene expression studies on the same tissues, 42% were differentially expressed when comparing pregnant and cycling animals and 11% were differentially expressed comparing pregnant fertile and sub-fertile animals. DNA methylation status was correlated with gene expression in several pathways implicated in early pregnancy events. Although these data do not provide direct evidence of a causative association between DNA methylation and gene expression, this study provides critical support for an effect of DNA methylation in early pregnancy events and highlights candidate genes for future studies.
Project description:Co-ordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A non-receptive uterine environment may be a key contributor to pregnancy loss, as the majority of pregnancy losses occur prior to embryo implantation. DNA methylation has been highlighted as a potential contributor in regulating early pregnancy events in the uterus. It was hypothesized that DNA methylation regulates expression of key genes in the uterus during pregnancy. To gain support for this hypothesis the correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and sub-fertile dairy cow strains were obtained at day 17 of pregnancy or the reproductive cycle. Microarrays were used to characterize genome-wide DNA methylation profiles and data compared with transcription profiles which have been previously reported. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. The 1,000 most significant correlations were used for subsequent analysis. Of these, 52% percent were negatively correlated with gene expression. When this gene list was compared with previously reported gene expression studies on the same tissues, 42% were differentially expressed when comparing pregnant and cycling animals and 11% were differentially expressed comparing pregnant fertile and sub-fertile animals. DNA methylation status was correlated with gene expression in several pathways implicated in early pregnancy events. Although these data do not provide direct evidence of a causative association between DNA methylation and gene expression, this study provides critical support for an effect of DNA methylation in early pregnancy events and highlights candidate genes for future studies. The estrous cycles of 24 lactating dairy cows were synchronized (at 58.8 (SEM 3.77) and 60.2 (SEM 1.51) days post calving in dairy cows of sub-fertile and fertile strains, respectively) and 14 received a single embryo transferred on day 7 of the estrous cycle. Animals were slaughtered at day 17 of the reproductive cycle and endometrial tissues (both caruncular and intercaruncular) were sampled. Selection criteria for the study included strain and calving date, and health postcalving was an exclusion criterion (cows with severe uterine infections or mastitis were excluded before being enrolled in the embryo transfer round). Cows in each strain were matched for calving number and age. A total of 10 cycling and 12 pregnant animals enrolled in the study were utilized, due to the associated costs of slaughtering the cows. These animals represented fertile (six pregnant and five cycling Holstein-Friesian cows with New Zealand ancestry/M-bM-^IM-$30% North American genetics, n=11, NZ) and sub-fertile (six pregnant and five cycling Holstein-Friesian cows with >87% North American ancestry, n=11, NA) phenotypes of Holstein-Friesian dairy cows
Project description:Genome wide placental DNA methylation profiling of full term and preterm deliveries sampled from 5 full term deliveries and 4 preterm deliveries. The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in formalin fixed samples. Samples included 4 placental tissues from 4 women with preterm delivery and 5 placental tissues from 5 women with full term delivery. 9 women's placental DNA (4 women had perterm deliveries and 5 women had full term deliveries) were hybridised to the Illumina HumanMethylation450 Beadchip
Project description:DNA methylation is an essential epigenetic mechanism involved in cell differentiation, proliferation, apoptosis, and metabolism. However, the DNA methylation changes of related genes during early pregnancy in dairy cows remain unclear . The purpose of this study was to study DNA methylation-related changes in early pregnancy cows and construct gene pools associated with pregnancy. In this study, we used peripheral blood samples from 15 healthy, productive and similar cows at 30 days post-breeding (Pre30) and 10 non-pregnant cows (Ctrl) and association analysis was performed using Reduced Representation Bisulfite Sequencing (RRBS) and transcriptomic sequencing methods. Targeted bisulfite sequencing (TBS) and Quantitative Real-time PCR (RT-qPCR) method are used to verify the Methylation differential genes. Our findings showed that DNA methylation majorly occurred in the cytosine-guanine (CG) range, and the amount of hypomethylation was higher than that of hypermethylation in 3Utrs, introns and promoters. A total of 76530 differentially methylated sites (DMCs) and 16411 differentially methylated regions (DMRs) were identified. RNA-seq identified 8858 differentially expressed genes (DEGs), with 4499 down-DEGs and 4359 up-DEGs. However, there were 44 significant differentially expressed genes, including 25 up-DEGs and 19 down-DEGs. DMC gene ontology (GO) analysis revealed significant enrichment in developmental process, cell differentitaion and nevous system development in biological processes (BP);Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated significant enrichment in cancer overview and cellular and Gastric cancer and Immune disease signaling pathways. DMRs GO analysis highlighted significant enrichment in the developmental process, cell differentiation and nervous system development; KEGG the results showed that significant enrichment in Signaling pathways regulating pluripotency of stem cells, Systemic lupus erythematosus,Transcriptional misregulation in cancer,Spliceosome,Herpes simplex virus 1 infection, Maturity onset diabetes of the young. DEG GO analysis results show that the main enrichment in BP differentiation of bone marrow cells, red blood cell differentiation and erythrocyte steady-state and anion during transportation and transshipment; KEGG analysis mainly concentrated in retinol metabolism, purine metabolism, cAMP signaling pathway and Gap junction pathway. Through a comprehensive analysis of RRBS and transcriptomics, 12 genes, including HBB, HBA 1, GPR 4, CPXM 2, SLC20A2, AFAP 1 and DOK 7, were different both in the methylome and the transcriptome. Early pregnancy changes in DNA methylation were significant and mainly down-regulated. These results can be the epigenetic changes in early pregnancy for cows provide new insights.
Project description:Early life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed before transcriptional changes in fetal liver in response to maternal folate depletion and hypothesised that these changes are due to altered gene promoter methylation. Female C57BL/6J mice were fed diets containing 2âmg or 0.4âmg folic acid/kg for 4âweeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers.