Endometrial zinc transporter Slc39a10/Zip10 is indispensable for progesterone responsiveness and successful pregnancy in mice
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ABSTRACT:
PROVIDER: PRJNA1059639 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the molecular mechanism underlying zinc transporter in the endometrium during embryo implantation, we generated mice with uterine-specific deletion of one of zinc transporter, Zip10. We report the sequencing of the uterine transcriptome of control and uterine-specific Zip10-deficient mice at day 4 (1600h) of pregnancy.
2025-02-10 | GSE252322 | GEO
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. We used microarrays to identify putative PGR-regulated genes in granulosa cells at a time when PGR expression is maximal (eCG + 8h hCG) and the preovulatory follicle is undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92437 | GEO
Project description:Epidemiological studies have shown that a full-term pregnancy at early age can decrease the breast cancer risk up to one-half. Pregnancy has been shown to prevent carcinogen-induced mammary tumors in rodents as well. The protective effect of pregnancy can be mimicked by administration of estrogen and progesterone to nulliparous rodents in amounts that are similar to those during pregnancy and alters responsiveness of p53 to DNA damage. Ovariectomized mice were treated with estrogen (E), progesterone (P), both estrogen and progesterone (E + P), or vehicle (V) alone and global expression profiles was analyzed to identify the mechanisms by which estrogen and progesterone combine to sensitize p53 function. Keywords: comparative hormone treatment
2008-07-31 | GSE5483 | GEO
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. Although PGR is not expressed in the cumulus cells or oocyte of the preovulatory cumulus oocyte complex (COC), it is well known that the COC responds to the cascade of gene expression changes that occurs in preovulatory granulosa cells. We used microarrays to identify putative ‘ovulation’ genes in preovulatory COCs at a time when PGR expression is maximal in granulosa cells (eCG + 8h hCG) and the preovulatory COC and follicle are undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92436 | GEO
Project description:Embryonic and fetal development can be affected during gestation by exposure to xenobiotics that cross the placenta. Liquid crystal monomers (LCMs) are emerging contaminants commonly found in indoor environments; however, whether they can cross the placenta and affect placental development remains unexplored. Here, we developed an evaluation system that integrates human biomonitoring, uterine perfusion in pregnant rats, and placental cells. We found fourteen out of the fifty-six LCMs that were detected in maternal and cord serum samples from ninety-three healthy pregnant women, at median levels of 13.9 and 18.1 ng/mL, respectively. Subsequent exploration of in utero exposure in rats indicated that aromatic amino acid transporter 1 (SLC16A10) mediated transplacental transportation of the LCMs. Placental cells exposed to LCMs exhibited delayed placental development and reduced progesterone release. These findings showed that SLC16A10-mediated transplacental transportation of LCMs inhibits placental development and progesterone release, highlighting the importance of gestational exposure to emerging contaminants.
2025-01-21 | PXD059395 | Pride
Project description:Epidemiological studies have shown that a full-term pregnancy at early age can decrease the breast cancer risk up to one-half. Pregnancy has been shown to prevent carcinogen-induced mammary tumors in rodents as well. The protective effect of pregnancy can be mimicked by administration of estrogen and progesterone to nulliparous rodents in amounts that are similar to those during pregnancy and alters responsiveness of p53 to DNA damage. Ovariectomized mice were treated with estrogen (E), progesterone (P), both estrogen and progesterone (E + P), or vehicle (V) alone and global expression profiles was analyzed to identify the mechanisms by which estrogen and progesterone combine to sensitize p53 function. Experiment Overall Design: Twenty ovariectomized animals were used for examine transcriptional effects of hormones by microarray. The hormones were administered by daily i.p. injection for 4 days.Treatment groups included: 4 animals receiving 2ug 17-beta-estrogen (E), 4 animals receiving 1mg progesterone (P), 5 animals receiving both estrogen and progesterone (E+P) and 4 animals receiving 100ul sesame oil (V). Epithelial-free fat pads from 3 animals receiving E+P were also analyzed to distinguish responses to E+P in the stroma (E+P CFP). Lymph nodes were removed from mammary glands at the time of collection.
2008-10-18 | E-GEOD-5483 | biostudies-arrayexpress
Project description:Uterine leiomyomas (LM) affect up to 80% of all reproductive-age women. LM growth requires progesterone, progesterone receptor (PGR), and the maintenance and proliferation of a small (5%) stem cell population. Stem cell activation and differentiation are driven by DNA methylation and nuclear hormone receptor action, but crosstalk between these mechanisms remains unclear. We performed an integrated analysis of the transcriptome and epigenetic landscape of LM cells at three differentiation stages and the PGR cistrome of whole LM tissue. The PGR-deficient stem cell population harbored a unique methylation landscape, with hypermethylation at the PGR gene locus and PGR-binding regions, which suppressed stem cell responsiveness to progesterone. The DNA methylation inhibitor 5’-Aza upregulated the expression of PGR and its target genes by stimulating PGR recruitment to the targeted gene loci, and significantly depleted the LM stem cell population and its tumor-initiating capacity. We herein provided mechanistic insights via therapeutically accelerating the stem cell differentiation process of a hormone-sensitive tumor.
2021-08-01 | GSE148256 | GEO
Project description:Uterine leiomyomas (LM) affect up to 80% of all reproductive-age women. LM growth requires progesterone, progesterone receptor (PGR), and the maintenance and proliferation of a small (5%) stem cell population. Stem cell activation and differentiation are driven by DNA methylation and nuclear hormone receptor action, but crosstalk between these mechanisms remains unclear. We performed an integrated analysis of the transcriptome and epigenetic landscape of LM cells at three differentiation stages and the PGR cistrome of whole LM tissue. The PGR-deficient stem cell population harbored a unique methylation landscape, with hypermethylation at the PGR gene locus and PGR-binding regions, which suppressed stem cell responsiveness to progesterone. The DNA methylation inhibitor 5’-Aza upregulated the expression of PGR and its target genes by stimulating PGR recruitment to the targeted gene loci, and significantly depleted the LM stem cell population and its tumor-initiating capacity. We herein provided mechanistic insights via therapeutically accelerating the stem cell differentiation process of a hormone-sensitive tumor.
2021-08-01 | GSE138050 | GEO
Project description:We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood, but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation.
2012-03-02 | GSE22025 | GEO
Project description:Different progesterone levels and timing of exposure results in different endometrial gene expression and implantation potential. Sufficient progesterone level is important to induce endometrial receptivity and endometrial expressed the most receptive stage after exposure to progesterone for 7 days based on decidualisation marker expression.
2020-03-12 | GSE146777 | GEO