MiR-29c-3p Impairs the Adhesion of Endometrial Epithelial Cells via COL4A1/β-catenin in Endometriosis.

OBJECTIVE

Defective endometrial receptivity is an indispensable cause of infertility in endometriosis, yet the post-transcriptional regulatory mechanisms underlying this impairment remain poorly understood. The goal of this research was to describe how miR-29c-3p and its target, COL4A1, regulate endometrial epithelial cell function and embryo adhesion.

METHODS

Endometrial epithelial cells were obtained from 14 women (including 7 with endometriosis and 7 controls) undergoing in vitro fertilization (IVF). Expression levels of miR-29c-3p and COL4A1 were quantified. Gain- and loss-of-function tests were employed in Ishikawa cells to assess cell adhesion capabilities and delineate downstream signaling pathways implicated in implantation.

RESULTS

Women with endometriosis had considerably higher levels of miR-29c-3p expression in their endometrial epithelium. Mechanistically, increased expression of miR-29c-3p suppressed COL4A1, downregulated E-cadherin, and impaired JAr spheroid attachment. Notably, COL4A1 knockdown recapitulated these phenotypes by encouraging epithelial-mesenchymal transition (EMT), thereby compromising adhesive capacity.

CONCLUSION

Our findings identify the miR-29c-3p/COL4A1/β-catenin axis as a pivotal hub controlling endometrial epithelial adhesion. In patients with endometriosis, this axis could be a potential molecular candidate to enhance fertility outcomes and restore endometrial receptivity.