Normal early pregnancy: a transient state of epigenetic change favoring hypomethylation
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ABSTRACT: The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared to both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared to non-pregnant states; there is no apparent permanent methylation imprint after a normal-term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform.
Project description:The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared to both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared to non-pregnant states; there is no apparent permanent methylation imprint after a normal-term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy.
Project description:Embryo-maternal signaling during the establishment of pregnancy in horses remains one of the biggest mysteries in large animal physiology. Early pregnancy loss represents a major source of economic loss to the breeding industry. This study aimed to investigate the systemic changes associated with early pregnancy by mapping the proteome of blood plasma in commercially bred pregnant (n = 17) and non-pregnant (n = 17) Thoroughbred mares at 14 days after ovulation, using high resolution mass spectrometry. We identified 229 total protein IDs, with 12 increased and 10 decreased significantly in pregnant vs non-pregnant plasma. To gain functional insight, these data were aligned with proteomes of 14-day pregnant mare uterine fluid (n = 4; 1,358 IDs) and conceptus fluid (soluble proteins within the yolk sac fluid; n = 4; 1,152 IDs), and further interrogated using gene ontology databases and pathway analysis. These analyses identified consistent systemic changes in the mare’s proteome that indicate a profound and specific immune response to early pregnancy, which appears to precede the systemic endocrine response to pregnancy. Integrated pathway analysis suggests that embryo-maternal interactions in early pregnancy may mimic elements of the virus-host interaction to modulate the maternal immune response. Transthyretin (TTR) and uteroglobin (SCGB1A1) were respectively down- and up-regulated in plasma while also present in uterine fluid, and are proposed to be key proteins in early pregnancy establishment. These findings contribute significantly to our knowledge of early pregnancy in the mare and identify new avenues for developing clinical approaches to reduce early embryo loss.
Project description:We performed a LC-FAIMS-MS proteomics of early pregnancy (11–14 weeks of gestation) serum from the pregnant women who developed preeclampsia (n = 11) and those from the noraml pregnant women (n = 12).
Project description:DNA methylation profiles were generating using Illumina HM450 microarrays in a prospective sample blood from the prenatal period of pregnant mood disorder patients who would and would not develop depression post partum. We recruited 54 pregnant women with a history of either Major Depression or Bipolar Disorder (I, II or NOS) and prospectively followed them during pregnancy and after delivery in order to identify genetic and clinical characteristics that precede the development of a postpartum depressive episode. Blood samples profiled were collected at varying time points during pregnancy.
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:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.
Project description:To explore the influence of choline intake and pregnancy status on gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed between two choline intake groups and between pregnant and non-pregnant women. Healthy third trimester (gestational week 26-29) pregnant women and non-pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6 pregnant and n=5 non-pregnant) or 930 (n=6 pregnant and n=5 non-pregnant) mg choline/d. Fasting peripheral blood leukocyte samples were collected at week 0 and week 12 to extract RNA and perform the arrays. Healthy third trimester (gestational week 26-29) pregnant women and non-pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6 pregnant and n=5 non-pregnant) or 930 (n=6 pregnant and n=5 non-pregnant) mg choline/d for 12 weeks. Fasting (10-h) peripheral blood leukocyte gene expression were measured at week 0 and week 12.
Project description:This study was done to identify endometrial DNA methylation marks that can be associated with pregnancy outcomes in postpartum cows at the time of breeding. Results showed that postpartum cows that could become pregnant could be distinguishable based on their endometrial DNA methylation patterns at the time of breeding.
Project description:Epigenetics may play a central, but yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy. We investigated changes in the methylome in isolated circulating CD4+ T cells in non-pregnant and pregnant women, during the 1st and 2nd trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with thousands of methylation differences, particularly during the 2nd trimester, where the majority of sites were hypermethylated, indicating transcriptional repression. Using a network-based modular approach disclosed several genes and pathways related to T cell signalling and activation. The pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. The directionality of the changes was also in line with the previously observed effect of pregnancy on the disease activity, with a negative correlation for multiple sclerosis and rheumatoid arthritis that improves during pregnancy, and a positive correlation for systemic lupus erythematosus, a disease that instead worsens. In summary, this systems medicine approach supports the importance of the methylome in immune regulation of CD4+ T cells during pregnancy. Samples included twelve (n=12) non-pregnant women, elven (n=11) 1st trimester pregnant women and twelve (n=12)