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Updated: Jul 10, 2026
Establishing a Mouse Model of Thin Endometrium
Published on: November 1, 2024
LGR5 as a therapeutic target for decidualization-based endometrial mesenchymal stem cells therapy in thin endometrium
Kai Chen1, Xueqing Ning1, Huiru Wang1
1Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 17 Lujiang Road, Luyang District, Hefei, 230001, China.
Background:
Decidualization of endometrial mesenchymal stem cells (ESCs) is crucial for the implantation of the embryo. Thin endometrium (TE) can impair endometrial receptivity by affecting the decidualization of ESCs. However, how TE affects the decidualization of ESCs remains unclear.
Methods:
Through multiple transcriptome analyses, we found that LGR5 plays a crucial role in the decidualization of ESCs. In vitro, siRNA was used to knock down LGR5 in ESCs, and decidualization was assessed via morphology, qRT-PCR, Western blot, and ELISA for decidualization marker (PRL, IGFBP-1). Colony forming assay, EdU, CFSE, and tube formation were used to evaluate proliferation and secretion. Signaling pathway components (β-catenin, AXIN2, PGR) were analyzed. In vivo, an adeno-associated virus (AAV) delivered shRNA to knock down Lgr5 in mouse uterine to assess endometrial receptivity and pregnancy rates. A TE mouse model was established and treated with decidualized endometrial mesenchymal stem cells (DSCs) or LGR5-knockdown DSCs to evaluate therapeutic efficacy.
Results:
LGR5 was significantly upregulated during decidualization and downregulated in TE tissues. In vitro, LGR5 knockdown impaired DSCs' morphological transformation, reduced decidualization, restored proliferation, but diminished secretory function and angiogenic potential. Mechanistically, LGR5 knockdown suppressed the β-catenin pathway and downregulated progesterone receptor (PGR). In vivo, Lgr5 knockdown reduced endometrial thickness, receptivity markers (Lif, Hoxa10, Pgr), and embryo implantation numbers. Crucially, transplanting LGR5-knockdown DSCs into TE mice resulted in inferior restoration of endometrial structure, reduced angiogenesis, and lower pregnancy rates compared to DSCs.
Conclusion:
LGR5 plays an important role in ESCs decidualization and may contribute to the therapeutic efficacy of DSCs for TE repair, potentially through regulation of PGR via the β-catenin pathway. These results indicate that LGR5 represents a candidate target worthy of further investigation for developing function-restoring therapies in TE.
