Dynamin-2 regulates polarized endometrial secretion and epithelial adhesion.

Abstract

In brief: Endometrial receptivity is established through epithelial acquisition of secretory and adhesive competence across distinct endometrial regions. Here, we examined the localization and expression of dynamin-2 (DNM2) in fertile and primary infertile endometrium and evaluated its functional role in glandular secretion and epithelial cell adhesion. Abstract: Endometrial receptivity is established through a hormonally regulated transition from a proliferative, nonreceptive epithelial state to a secretory and adhesive phenotype during the midsecretory phase of the menstrual cycle. Failure of this transition results in implantation failure and infertility. However, the epithelial mechanisms coordinating secretion and adhesion remain poorly defined. We investigated the role of dynamin-2 (DNM2), a membrane-remodelling GTPase, in regulating human endometrial epithelial cell function. In fertile endometrium, DNM2 was upregulated during the midsecretory phase with compartment-specific localization, showing apical enrichment in glandular epithelium and basal localization in luminal epithelium. DNM2 expression and glandular enrichment were reduced in midsecretory endometrium from women with primary infertility. Using hormone-responsive endometrial epithelial organoids, we show progestin-dependent induction of DNM2 in fertile but not infertile epithelium. Inhibition of DNM2 activity selectively altered apical secretions, reducing proteins associated with extracellular signalling, immune regulation, and epithelial interaction. DNM2 knockdown in endometrial epithelial cells impaired trophoblast spheroid adhesion and reduced receptivity-associated gene expression, including STAT3 and SPP1. Together, these findings suggest a potential role for DNM2 in endometrial receptivity and reveal its dysregulation in unexplained infertility.