Myosin heavy chain 10 dysregulation in infertile endometrial epithelial cells impairs adhesive capacity

Endometrial receptivity occurs during a limited time in the menstrual cycle called the 'window of implantation' (WOI) and is required for successful implantation. Endometrial luminal epithelial cells become adhesive to facilitate embryo attachment and implantation; however, how this occurs is poorly understood. We recently identified that myosin heavy chain 10 (MYH10) was abnormally downregulated in infertile organoid endometrial epithelial cells during the WOI, suggesting a role in receptivity. MYH10 regulates cell polarity, adhesion and migration; however, whether it regulates receptivity is unknown. Our research investigated whether MYH10 regulates endometrial epithelial cell adhesive capacity. MYH10 is localized to all major cellular compartments within the endometrium. Immunostaining intensity was higher in luminal epithelial cells during the WOI compared to the proliferative phase in fertile endometrium. However, MYH10 staining was decreased in infertile endometrium. siRNA knockdown of MYH10 in the Ishikawa cell line significantly decreased cell adhesion to human cytotrophoblast-progenitor spheroids. MYH10 knockdown increased PGR and FOXO1 while decreasing PDLIM2 expression. Proteomics analysis following MYH10 knockdown demonstrated altered production of 57 proteins with functions critical in receptivity, including tight junctions. These results demonstrate that MYH10 alters endometrial epithelial cell adhesive capacity primarily via regulation of the actin cytoskeleton, implying an important role in implantation.