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The impact of pregnancy experience on uterine gene expression and decidualization

ABSTRACT: To capture the global gene changes associated with pregnancy experience, uterine tissues were collected on day 8 of pregnancy from mice during the first pregnancy and second pregnancy, respectively. Transcriptomes were determined by RNA-seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE69018 | GEO | 2015/05/20

SECONDARY ACCESSION(S): PRJNA284380

REPOSITORIES: GEO

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The impact of pregnancy experience on uterine gene expression and decidualization

Project description:To capture the global gene changes associated with pregnancy experience, uterine tissues were collected on day 8 of pregnancy from mice during the first pregnancy and second pregnancy, respectively. Transcriptomes were determined by RNA-seq. Identifying global gene changes associated with pregnancy experience

2015-05-20 | E-GEOD-69018 | biostudies-arrayexpress

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EP001: The interferon transcriptome in uterine NK cells is upregulated during the second trimester of pregnancy allowing extravillous trophoblast invasion

Project description:Uterine Natural Killer (uNK) cells regulate essential developmental processes at the maternal-fetal interface during early pregnancy. Uterine NK cell functions are tightly regulated during early placentation to stimulate trophoblast invasion and remodel uterine spiral arteries. Access to human 1st and 2nd trimester uterine tissues allowed us to investigate the transcriptional changes in uNK cells during the early stages of early human pregnancy. Microarray analysis identified 97 upregulated genes in 2nd compared to 1st trimester purified uNK cells of which the majority (61%) clustered as interferon-stimulated-genes (ISG), with ISG15 and ISG20 being upregulated profoundly. Type I interferons (IFNα/β), but not type II interferon (IFNɣ) increased expression of the identified interferon target genes ISG15 and ISG20 in uNK cells in vitro. Moreover, the cytokine-like protein ISG15 stimulated in vitro trophoblast invasion. Second trimester uNK cells promoted trophoblast invasion in vitro, whereas both 1st and 2nd trimester uNK cells stimulated endothelial tube formation. IFNα but not IFNβ stimulation of 1st trimester uNK cells enhanced their capacity to promote trophoblast invasion. In conclusion, the uNK cell interferon transcriptome is upregulated during the 2nd trimester allowing uNK cells to promote trophoblast invasion. Type I interferon signaling regulates uNK cell-induced trophoblast invasion via induction of effector molecules like ISG15. First trimester uNK cells can be induced to act like second trimester uNK cells by IFNα with respect to promotion of trophoblast invasion. Key words: Gene expression profiling ■ uterine natural killer cells ■ extravillous trophoblast invasion ■ interferon alpha ■ ISG15

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Project description:We demonstrate that Sirtuin 1 (SIRT1) is an indispensable age-related regulator of invasion and spacing of blastocysts, as well as decidualization of stromal cells. Here, we report the sequencing of the uterine transcriptome of control and conditional knock-out of the Sirtuin 1 (SIRT1) at day 3.5 of murine pregnancy.

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H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition [RNA-seq]

Project description:Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a non-contractile state until term and then surmounts this state to enter labor. Here, we show in mice that dynamic deposition and removal of repressive H3K27me3 chromatin marks in decidual stromal cells dictate both elements of pregnancy success. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets insures uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and, most unexpectedly, generating myofibroblasts and associated wound healing responses. In late gestation, genome-wide H3K27 demethylation allows for target gene upregulation, decidual activation, and labor entry. Strikingly, pharmacological inhibition of this latter process not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a non-inflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.

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