3 minute lightning oral presentation (and poster) ESA-SRB 2023 in conjunction with ENSA

Myosin Heavy Chain 10 downregulation within endometrial epithelial cells contributes to dysregulation in adhesion (#201)

Michaela Sacco 1 2 , Wei Zhou 1 2 , Poppy Downing 1 2 , Wan Tinn Teh 2 3 4 5 , Evdokia Dimitriadis 1 2
  1. Gynaecology Research Centre, Royal Women's Hospital, Melbourne, Victoria, Australia
  2. Department of Obstetrics, Gynaecology and Newborn Health, The University of Melbourne, Melbourne, Victoria, Australia
  3. Reproductive Services, Royal Women's Hospital, Melbourne, Victoria, Australia
  4. Melbourne IVF, Melbourne, Victoria, Australia
  5. Epworth HealthCare, Melbourne, Victoria, Australia

Endometrial receptivity is defined as the functional, morphological, and molecular changes of the endometrium during the window of implantation that facilitate blastocyst implantation. Luminal epithelial cell adhesive capacity is crucial for successful blastocyst attachment and implantation. Poor endometrial receptivity contributes to weak adhesion, implantation failure, and infertility. Despite this effect upon fertility, there is a lack of knowledge required to develop diagnoses and treatments. Our recent proteomics screen using an endometrial epithelial organoid model has identified a correlation between Myosin Heavy Chain 10 (MYH10) downregulation and infertility. MYH10 is a conventional non-muscle myosin and actin-dependent motor protein. Via actin cytoskeleton, MYH10 regulates cell polarity, adhesion, and migration; factors which may contribute to proper endometrial function. This study aimed to understand the role of MYH10 in endometrial receptivity. Investigation of MYH10 via immunohistochemistry revealed expression within glandular epithelium, luminal epithelium, and stroma. Fertile endometrium exhibited significantly higher MYH10 expression within glandular and luminal epithelial cells during the mid-secretory phase compared to the proliferative phase (n=11, P<0.05). Further comparison between fertile and primary infertile endometrium during the mid-secretory phase revealed a significant decrease in MYH10 within infertile luminal epithelium (n=11, P<0.05). MYH10 knockdown in Ishikawa cells (receptive endometrial epithelial cell line) significantly reduced adhesive capacity as shown via a trophoblast spheroid adhesion assay (n=4, P<0.05). xCELLigence real-time monitoring demonstrated decreased cellular proliferation in response to MYH10 knockdown compared to controls (n=10, P<0.0001). To elucidate the mechanistic pathways by which MYH10 regulates endometrial receptivity, qPCR assessed expression of endometrial receptivity and actin cytoskeleton associated genes. Results demonstrated significantly differential expression of PGR and PDLIM2, respectively, compared to controls (n=8, P<0.05). These results convey the potential importance of MYH10 in regulation of endometrial epithelial cell adhesion, partly via regulation of actin cytoskeleton genes, therefore implying a role in implantation.