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.
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. 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: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: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:The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endo- metria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h (P < 0.05). On day 13 following estrous endometrial expression of nine genes increased [ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven genes decreased (SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, MGC128929, and WBSCR17; P < 0.05) in pregnant compared with cyclic heifers. Of these DEGs, significant differences in expression between pregnant and cyclic endometria were maintained on day 16 for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, and ZSWIM4 (P < 0.05) both their expression was not directly regulated by IFNT in vivo. Analysis of the expression of selected interferon-stimulated genes in blood samples from postpartum dairy cows revealed a significant increase (P < 0.05) in expression of ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared with cyclic controls. In conclusion, RNAseq identified a number of novel pregnancy-associated genes in the endometrium of cattle during early pregnancy that are not regulated by IFNT in vivo. In addition, a number of genes that are directly regulated by short term exposure to IFNT in vivo are differentially expressed on day 18 following estrus detection in the blood of postpartum dairy cows depending on their pregnancy status. mRNA profiles of pregnant vs not pregnant cross-bred beef heifers at days 13 and 16 (n=5 per group)
Project description:During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta-cells. However, the exact mechanisms by which the lactogenic hormones drive beta-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive beta-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in beta-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes. Analysis of poly(A)+ RNA from 3 biological replicates of pancreatic islets isolated from normal female and pregnant female mice
Project description:The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endo- metria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h (P < 0.05). On day 13 following estrous endometrial expression of nine genes increased [ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven genes decreased (SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, MGC128929, and WBSCR17; P < 0.05) in pregnant compared with cyclic heifers. Of these DEGs, significant differences in expression between pregnant and cyclic endometria were maintained on day 16 for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, and ZSWIM4 (P < 0.05) both their expression was not directly regulated by IFNT in vivo. Analysis of the expression of selected interferon-stimulated genes in blood samples from postpartum dairy cows revealed a significant increase (P < 0.05) in expression of ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared with cyclic controls. In conclusion, RNAseq identified a number of novel pregnancy-associated genes in the endometrium of cattle during early pregnancy that are not regulated by IFNT in vivo. In addition, a number of genes that are directly regulated by short term exposure to IFNT in vivo are differentially expressed on day 18 following estrus detection in the blood of postpartum dairy cows depending on their pregnancy status.
Project description:In order to systematically analyze the maternal, i.e. the endometrial, changes in the equine endometrium underlying the complex embryo-maternal dialogue during early pregnancy, a transcriptome study of endometrium samples from five mares at day 8 and six mares at day 12 of early pregnancy and the corresponding non-pregnant stage was performed. Endometrial biopsies were taken from six warmblood mares at day 12 of early pregnancy after embryo recovery and at the corresponding non-pregnant stage. 12 samples were analyzed: one pregnant sample and the corresponding control sample of every mare each at a time. Endometrial biopsies were taken from five warmblood mares at day 8 of early pregnancy after embryo recovery and at the corresponding non-pregnant stage. 10 samples were analyzed: one pregnant sample and the corresponding control sample of every mare each at a time. Two experimental groups: 8 and 12 days
Project description:Pancreatic β-cell mass expands during pregnancy and regresses in the postpartum period in conjunction with dynamic metabolic demands on maternal glucose homeostasis. To understand transcriptional changes driving these adaptations in β-cells and other islet cell types, we performed single-cell RNA sequencing on islets from virgin, late gestation, and early postpartum mice. We identified transcriptional signatures unique to gestation and the postpartum in β-cells, including induction of the AP-1 transcription factor subunits and other genes involved in the immediate-early response (IEGs). Additionally, we found pregnancy and postpartum-induced changes differed within each endocrine cell type, and in endothelial cells and macrophages within islets. Together, our data reveal novel insights into cell-type specific transcriptional changes responsible for adaptations by islet cells to pregnancy and their resolution postpartum.
Project description:To identify the molecular markers of early pregnancy in pigs, we compared global gene expression profiles of the maternal peripheral blood in pregnant sows with the non-pregnant sows. Peripheral blood sample was collected at 14 days after insemination from the submandibular vein of pregnant and non-pregnant sows respectively, and total RNA was isolated, purified and sent for microarray analysis. This study identified 127 up-regulated and 56 down-regulated genes (FC >= 1.5 and P < 0.05) in peripheral blood from pregnant sows versus non-pregnant sows. Of the differently expressed genes, nine (including LPAR3, RXFP4, GALP, CBR1, CBR2, GPX6, USP18, LHB and NR5A1) were found to exert function related to early pregnancy processes. Seven differentially expressed genes (CHGB, USP18, VWF, LPAR3, NR5A1, PPARD, BIN1) were selected to perform qRT-PCR in the same RNA samples.The expression profiles of these genes detected by qRT-PCR were consistent with those by microarray, which confirmed the reliability of our microarray data.
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.