SCGB2A1 deficiency impairs endometrial stromal cell decidualization by decreasing CDK3-mediated proliferation in patients with recurrent implantation failure
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ABSTRACT:
PROVIDER: PRJNA1121401 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29325504_1.fastq.gz | Fastqsanger.gz | |||
| SRR29325504_2.fastq.gz | Fastqsanger.gz | |||
| SRR29325505_1.fastq.gz | Fastqsanger.gz | |||
| SRR29325505_2.fastq.gz | Fastqsanger.gz | |||
| SRR29325506_1.fastq.gz | Fastqsanger.gz |
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Project description:Recurrent implantation failure (RIF) presents a significant challenge in the field of assisted reproductive technology, primarily stemming from compromised decidualization that impacts endometrial receptivity. Despite ongoing research efforts, the comprehensive molecular regulatory mechanisms involved in RIF remain incompletely understood. This study revealed significantly reduced levels of secretoglobin, family 2A, member 1 (SCGB2A1) in both the mid-secretory endometrium and uterine fluid of RIF patients compared to control subjects. Besides, combined with RNA sequencing results, we demonstrated that the suppression of SCGB2A1 results in reduced cell proliferation and impaired decidualization by modulating CDK3 signaling during cell cycle transition in immortalized human endometrial stromal cells (T-HESCs) and primary HESCs. Furthermore, our findings indicated that inhibition of endometrial SCGB2A1 in a rat model hinders embryo implantation and disrupts decidualization. In conclusion, this study provides evidence that SCGB2A1 serves as a novel biomarker for endometrial receptivity and plays a crucial role in the regulation of human endometrial decidualization. The findings offer valuable insights into the pathogenesis of decidualization-related RIF and have the potential to enhance strategies for improving pregnancy outcomes.
2025-01-01 | GSE269408 | GEO
Project description:Proper decidualization is vital in preparation for a potential embryo receptivity, placentation, menstrual health and subsequent endometrial regeneration. Given the importance of extracellular vesicles (EVs) in intercellular communication, and recently in embryo implantation and indicators of menstrual cycle and fertility, we investigated their role during decidualization. Overall, this study provides an insight into distinct variation in sEV composition depending upon the level of decidualization of endometrial stromal cells, with the signaling potential to coordinate endometrial health ranging from embryo implantation, facilitating placentation and subsequent endometrial regeneration.
2021-11-17 | PXD026342 | Pride
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
Project description:Recurrent implantation failure(RIF) is an urgent problem to be solved in reproduction.Currently, endometrium decidualization damage is considered as one of the important causes, but the mechanism is still unclear. Prokineticin 2(PK2) is a newly discovered secreted protein with multiple biological functions, and its role in the endometrium is unknown.Our previous study showed that PK2 was significantly increased in RIF patients, but endometrial decidualization markers PRL and IGFBP1 were lower compared with the control group. We performed transcriptome sequencing, we found there were significant differences between the PK2 overexpression group and the control group. Differential genes mainly involved in decidualization process including adhesion, immunity, chemotaxis, ect.
2020-12-29 | GSE163936 | GEO
Project description:Patient-control group project investigating recurrent failure of embryo-implantation by expression analysis of endometrium biopsies
2015-12-31 | E-MTAB-2591 | biostudies-arrayexpress
Project description:We aimed to identify altered biological processes in the endometrium that may be potential markers of receptive endometrium. RNA expression profiling of the endometrium during the window of implantation was performed in patients with Recurrent Implantation Failure (RIF) versus fertile controls.
2018-03-18 | GSE111974 | GEO
Project description:Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects. Eight samples were analyzed: derived from four control and four recurrent pregnancy loss (RPL) patient cultures.
2015-09-16 | E-GEOD-65100 | biostudies-arrayexpress
Project description:BackgroundThe precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF.MethodsMid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation.ResultsThe expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth.ConclusionThe reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.
| S-EPMC9756673 | biostudies-literature
Project description:BackgroundDecidualization is a prerequisite for successful implantation and the establishment of pregnancy. A critical role of impaired decidualization in subfertility has been established. In human endometrial stromal cells (hESCs), Krüppel-like factor 12 (KLF12) and Nur77 are novel regulators of decidualization. We investigated whether KLF12 impaired the decidualization of hESCs in recurrent implantation failure (RIF) patients.MethodsEndometrial tissues and hESCs were collected from RIF patients (n = 34) and fertile controls (n = 30) for in vitro analysis. Primary hESCs isolated from RIF endometrial tissues were used to evaluate the biological functions of KLF12 and Nur77. In addition, their molecular mechanisms were investigated by adenovirus-mediated overexpression. Gene expression regulation was examined by real-time-quantitative PCR (qRT-PCR), immunostaining and luciferase reporter assay. Further, blastocyst-like spheroid (BLS) and blastocyst implantation models were performed to examine the roles of KLF12 and Nur77 during embryo expansion on hESCs.ResultshESCs from the RIF patients showed a poor decidual response, mainly characterized by decreased decidual prolactin (dPRL) secretion, impaired transformation and limited BLS expansion. In addition, KLF12 expression was increased in endometrial tissues from the RIF patients compared with those from the fertile controls, especially in stromal compartments. The opposite results were observed for Nur77 expression in these tissues. KLF12 repressed hESC decidualization by decreasing Nur77 expression. Mechanistically, KLF12 bound to a conserved site in the Nur77 promoter region. Nur77 overexpression significantly reversed the KLF12-mediated repression of dPRL expression, decidual transformation and BLS/blastocyst expansion.ConclusionsKLF12 impairs endometrial decidualization by transcriptionally repressing Nur77, and Nur77 overexpression reverses the poor decidual response of hESCs in RIF patients.
| S-EPMC5374626 | 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.
2022-06-06 | GSE205084 | GEO