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Objective: Approximately 15% of couples of reproductive age experience infertility. In vitro fertilization (IVF) is the most useful treatment for patients with infertility. However, repeated implantation failure (RIF) is one of the most difficult challenges for the success of IVF, caused by poor endometrial receptivity due to decreased endometrial cell proliferation. This study aimed to investigate the mechanism regulating endometrial cell proliferation to overcome RIF. Methods: Hub genes involved in RIF were identified by RNA sequencing for endometrial tissues. The regulatory effects of circular RNA (circRNA) and microRNA (miRNA) in human endometrial stromal cells (hESCs) were determined using miRNA pulldown and dual-luciferase reporter gene assays. Cell proliferation was detected using a Cell Counting Kit-8 assay. Results: G protein-coupled estrogen receptor 1 (GPER1) expression was dramatically downregulated in endometrial tissues obtained from patients with RIF, suggesting that GPER1 might be a hub gene involved in RIF. Additionally, circRNA SNX11 increases GPER1 expression via hsa-miR-1343-3p in hESCs. Additionally, circRNA SNX11 promotes cell proliferation, reduces apoptosis, and modulates RIF-related pathways through GPER1 by sponging hsa-miR-1343-3p in hESCs. Conclusion: This study reveals that circRNA SNX11 facilitates endometrial cell proliferation by upregulating GPER1 by sponging hsa-miR-1343-3p, providing novel therapeutic targets to overcome RIF.
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Shi et al. (2026) studied this question.
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