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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.
Insights
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is vital for endometrial mesenchymal stem cell (ESC) decidualization, impacting embryo implantation. Targeting LGR5 shows promise for treating thin endometrium (TE) and improving pregnancy rates.
Area of Science:
- Reproductive Biology
- Stem Cell Biology
- Genetics and Genomics
Background:
- Decidualization of endometrial mesenchymal stem cells (ESCs) is essential for successful embryo implantation.
- Thin endometrium (TE) compromises endometrial receptivity by hindering ESC decidualization, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the role of LGR5 in ESC decidualization and its potential as a therapeutic target for thin endometrium (TE).
- To elucidate the molecular mechanisms by which LGR5 influences decidualization and endometrial receptivity.
Main Methods:
- Transcriptome analysis identified LGR5 as crucial for ESC decidualization.
- In vitro studies utilized siRNA to knockdown LGR5 in ESCs, assessing decidualization markers, proliferation, secretion, and angiogenesis.
- In vivo studies employed adeno-associated virus (AAV)-mediated shRNA in a mouse model to evaluate Lgr5's effect on endometrial receptivity and pregnancy rates, and tested therapeutic efficacy using LGR5-knockdown DSCs in a TE mouse model.
Main Results:
- LGR5 expression was upregulated during decidualization and downregulated in TE tissues.
- LGR5 knockdown in vitro impaired ESC decidualization, altered proliferation and secretory function, and reduced angiogenic potential, suppressing the β-catenin pathway and PGR.
- In vivo, Lgr5 knockdown reduced endometrial thickness, receptivity markers, and embryo implantation. Transplanting LGR5-knockdown DSCs into TE mice showed inferior therapeutic effects compared to normal DSCs.
Conclusions:
- LGR5 is critical for ESC decidualization and contributes to the therapeutic potential of DSCs for TE repair, likely via PGR regulation through the β-catenin pathway.
- LGR5 emerges as a promising therapeutic target for developing function-restoring treatments for thin endometrium (TE).
