Myosin Heavy Chain 10 dysregulation in infertile endometrial epithelial cells impairs adhesive capacity

ABSTRACT: Endometrial receptivity is defined as the functional, morphological, and molecular changes of the endometrium occurring during a limited time period in the menstrual cycle called the ‘window of implantation’. The endometrial luminal epithelial cells are critical in producing this receptivity as their adhesive capacity enables embryo implantation; however, how this occurs is poorly understood. Recently, using endometrial epithelial organoids, we identified that Myosin Heavy Chain 10 (MYH10) was abnormally downregulated in infertile endometrial epithelial cells during the window of implantation, suggesting a role in receptivity. MYH10 regulates processes important in endometrial receptivity including cell polarity, adhesion, and migration; however, whether it regulates endometrial receptivity has yet to be researched. We aimed to investigate whether MYH10 regulates endometrial epithelial cell adhesive capacity. MYH10 localised to all major cellular compartments within endometrial tissue. However, immunostaining intensity was higher in luminal epithelial cells during the window of implantation compared to the proliferative phase in fertile endometrium. Conversely, this increased expression was not maintained in infertile endometrium during the window of implantation. siRNA knockdown of MYH10 in the receptive Ishikawa cell line significantly decreased cell adhesion to human cytotrophoblast-progenitor spheroids. MYH10 knockdown in Ishikawa cells also increased PGR, FOXO1, and GPX3 expression, while decreasing PDLIM2 expression. Proteomics analysis following MYH10 knockdown altered the production of 57 proteins with functions critical in endometrial receptivity including tight junction regulators. These results demonstrate that MYH10 alters endometrial epithelial cell adhesive capacity primarily via regulation of the actin cytoskeleton, implying an important role in implantation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Uterine Endometrium

DISEASE(S): Infertility

SUBMITTER: Michaela Sacco  

LAB HEAD: Evdokia Dimitriadis

PROVIDER: PXD062326 | Pride | 2026-05-05

REPOSITORIES: Pride