Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling.
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ABSTRACT:
SUBMITTER: George AF
PROVIDER: S-EPMC7105328 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:SP promotes decidualization of eSF from women with and without inflammatory disorders (polycystic ovarian syndrome (PCOS), endometriosis) in a manner that is not mediated through semen amyloids and that is associated with a potent transcriptional response including induction of IL11, a cytokine important for SP-induced decidualization.
2020-03-09 | GSE135640 | GEO
Project description:Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes. The data suggest the existence of an early signal transducer and activator of transcription (STAT) pathway dominated state and a later nuclear factor ?B (NFKB) pathway regulated state. Transcription factor expression in both phases is characterized by putative or known progesterone receptor ( PGR) target genes, suggesting that both phases are under progesterone control. Decidualization leads to proliferative quiescence, which is reversible by progesterone withdrawal after 3 days but to a lesser extent after 8 days of decidualization. In contrast, progesterone withdrawal induces cell death at comparable levels after short or long exposure to progestins and cAMP. We conclude that decidualization is characterized by a biphasic gene expression dynamic that likely corresponds to different phases in the establishment of the fetal-maternal interface.
| S-EPMC6728557 | biostudies-literature
Project description:Seminal plasma promotes decidualization of endometrial stromal fibroblasts from women with and without inflammatory disorders in a manner dependent on IL11 signaling
| PRJNA559534 | ENA
Project description:Seminal plasma (SP), the liquid fraction of semen, is not mandatory for conception, but clinical studies suggest that SP improves implantation rates. Prior in vitro studies examining the effects of SP on the endometrium, the site of implantation, surprisingly revealed that SP induces transcriptional profiles associated with neurogenesis. We investigated the presence and activity of neurogenesis pathways in the endometrium, focusing on TrkA, one of the canonical receptors associated with neurotrophic signaling. We demonstrate that TrkA is expressed in the endometrium. To determine if SP activates TrkA signaling, we isolated the two most abundant endometrial cell types-endometrial epithelial cells (eEC) and endometrial stromal fibroblasts (eSF)-and examined TrkA activity in these cells after SP exposure. While SP only moderately activated TrkA in eEC, it potently and rapidly activated TrkA in eSF. This activation occurred in both non-decidualized and decidualized eSF. Blocking this pathway resulted in dysregulation of SP-induced cytokine production by eSF. Surprisingly, while the canonical TrkA agonist nerve growth factor was detected in SP, TrkA activation was principally induced by a 30-100-kDa protein whose identity remains to be established. Our results show that TrkA signaling is highly active in eSF and is rapidly induced by SP.
| S-EPMC6084595 | biostudies-literature
Project description:Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor ( IGF)-1, Insulin-like growth factor binding protein ( IGFBP)-1, and PRL gene expression at baseline and during decidualization. These effects were mediated through protease activated receptor (PAR)-1- and PAR-1-independent pathways. Thrombin decreased the secretion of a key marker of decidualization (PRL), altered the morphological transformation of decidualizing hESCs, and activated genes involved in matrix degradation and proinflammatory chemokines ( Interleukin-8 and Interleukin-6). Genes encoding factors important for matrix stability ( Col1α1, LOX) were suppressed. We suggest that intrauterine bleeding and generation of thrombin accentuates leukocyte extravasation and endometrial inflammation, impairs decidualization, and endometrial support of early pregnancy.
| S-EPMC6728565 | biostudies-literature
Project description:Nucleotide-binding oligomerization domain (NACHT), leucine rich repeat (LRR) and pyrin domain (PYD) 7 containing protein, NLRP7, is a member of the NLR family which serves as innate immune sensors. Mutations and genetic variants of NLRP7 have been found in women with infertility associated conditions, such as recurrent hydatidiform mole, recurrent miscarriage, and preeclampsia. Decidualization of endometrial stromal cells is a hallmark of tissue remodeling to support embryo implantation and proper placental development. Given defective decidualization has been implicated in miscarriage as well as preeclampsia, we aimed to explore the link between the NLRP7 gene and decidualization.Endometrial samples obtained from pregnant women in the first trimester and non-pregnant women were used to study NLRP7 expression pattern. The human telomerase reverse transcriptase (hTERT)-immortalized human endometrial stromal cells (T-HESCs) were used to study the effect of NLRP7 on decidualization. Decidualization of T-HESCs was induced with 1 μM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). siRNA was used to knock down NLRP7 while lentiviral vectors were used to overexpress NLRP7 in cells. NLRP7 expression was detected by immunofluorescence, qRT-PCR, and Western blotting. Decidualization markers, Insulin-like growth factor-binding protein 1 (IGFBP-1) and prolactin (PRL), were detected by qRT-PCR and ELISA. Nuclear translocation of NLRP7 was detected by the subcellular fractionation and confocal microscopy. The effect of NLRP7 on progesterone receptor (PR) activity was evaluated by a reporter system.NLRP7 was up-regulated in the decidual stromal cells of human first-trimester endometrium. After in vitro decidualization, T-HESCs presented with the swollen phenotype and increased expressions of IGFBP-1 and PRL. Knockdown or over-expression of NLRP7 reduced or enhanced the decidualization, respectively, according to the expression level of IGFBP-1. NLRP7 was found to translocate in the nucleus of decidualized T-HESCs and able to promote PR activity.NLRP7 was upregulated and translocated to the nucleus of the endometrial stromal cells in an in vitro decidualization model. Overexpressed NLRP7 promoted the IGFBP-1 expression and PR reporter activation. IGFBP-1 expression decreased with the knockdown of NLRP7. Therefore, we suggest that NLRP7 contributes to in vitro decidualization of endometrial stromal cells.
| S-EPMC5558772 | biostudies-other
Project description:Infertility and early embryo miscarriage is linked to inadequate endometrial decidualization. Although transcriptional reprogramming is known to drive decidualization in response to progesterone, the key signaling effectors that directly mediate this hormone response are not fully known. This knowledge gap is clinically significant because identifying the early signals that directly mediate progesterone-driven decidualization will address some of the current limitations in diagnosing and therapeutically treating patients at most risk for early pregnancy loss. We recently revealed that the promyelocytic leukemia zinc finger (PLZF) is a direct target of the progesterone receptor and is essential for decidualization of human endometrial stromal cells (hESCs). The purpose of this current work was to identify the genome-wide transcriptional program that is controlled by PLZF during hESC decidualization using an established in vitro hESC culture model, siRNA-mediated knockdown methods, and RNA-sequencing technology followed by bioinformatic analysis and validation. We discovered that PLZF is critical in the regulation of genes that are involved in cellular processes that are essential for the archetypal morphological and functional changes that occur when hESCs transform into epithelioid decidual cells such as proliferation and cell motility. We predict that the transcriptome datasets identified in this study will not only contribute to a broader understanding of PLZF-dependent endometrial decidualization at the molecular level but may advance the development of more effective molecular diagnostics and therapeutics for the clinical management of female infertility and subfertility that is based on a dysfunctional endometrium.
| S-EPMC5819842 | biostudies-other
Project description:This study examined the effect of bisphenol A (BPA) exposure on human uterine stromal fibroblast cells (HuF) undergoing decidualization. HuF cells were isolated and cultured for eight days in the presence of a decidualization-inducing cocktail, while concurrently exposed to physiological and supra-physiologic doses of BPA (1ng/mL, 10ng/mL, 0.5?g/mL, 10?g/mL and 20?g/mL). Decidualization markers, steroid hormone receptors and cell cycle gene expression were detected by qRT-PCR and cellular proliferation was assessed by KI-67 immunofluorescent staining and MTS assay. BPA impaired decidualization at 10?g/mL and 20?g/mL, but not at lower doses. Additionally, BPA at 20?g/mL decreased progesterone receptor and estrogen receptor-alpha compared to controls. The highest dose of BPA also reduced cellular proliferation and cyclin D2 expression compared to controls. These findings demonstrate that BPA disrupts in vitro decidualization of uterine stromal fibroblasts by altering steroid hormone receptor expression at higher concentrations but not at lower physiological doses.
| S-EPMC5892434 | biostudies-literature
Project description:Human endometrium decidualization, which involves endometrial stromal proliferation and differentiation, is a prerequisite for embryo implantation, thus successful pregnancy. The Forkhead Box M1 (FoxM1), previously known as HNF-3, HFH-11, MPP2, Win, and Trident, is a transcriptional factor that plays crucial roles in cell proliferation and cell cycle progression. However, the molecular mechanism of FoxM1 during human endometrial decidualization remains unexplored. In this study, we first found FoxM1 is dynamically expressed in human endometrium during menstrual cycle. Employing a human endometrial stromal cell (HESC) line, we then demonstrated that FoxM1 inhibition downregulates cyclin B1 expression, delaying G2/M phase transition during HESC proliferation. Additionally, loss of FoxM1 expression blocks the differentiation of HESCs in response to estrogen, progesterone, and dbcAMP. Applying chromatin immunoprecipitation (ChIP) technique and luciferase assay, we further approved that FoxM1 can transcriptionally active signal transducer and activator of transcription 3 (STAT3), ensuring normal HESC differentiation. Besides enriching our knowledge on molecular basis underlying stromal decidualization, these findings help to shed light on the potential molecular causes for the endometrial disorders in humans.
| S-EPMC4558550 | biostudies-literature
Project description:Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are impacted by steroid hormones, estrogen and progesterone, as well as stroma-derived factors. Using an endometrial epithelial organoid (EEO) system, transcriptome and proteome analyses identified distinct responses of the EEO to steroid hormones and prostaglandin E2 (PGE2). Notably, steroid hormones and PGE2 modulated the basolateral secretion of EEO proteins, where cystatin C (CST3) was significantly increased by progesterone and PGE2. CST3 treatment of decidualizing stromal cells significantly decreased the decidualization markers PRL and IGFBP1. The attenuation of stromal cell decidualization via CST3 suggests a role for uterine gland-derived proteins in controlling the extent of decidualization. These findings provide evidence that uterine gland-derived factors directly impact stromal cell decidualization, which has strong implications for better understanding pregnancy establishment and female fertility in humans.
2023-10-11 | PXD034357 | Pride