Increased levels of testosterone associated with polycystic ovary syndrome negatively affect HOXA10 and integrin b3 expression in endometrial cells and embryo attachment using a trophoblast cell spheroid model
PCOS is a reproductive endocrine disorder that affects up to 10% of women of a reproductive age, with 70-80% of patients defined as infertile. There are many different symptoms that could impact fertility in women with PCOS such as anovulation, hyperandrogenism and insulin resistance.
A trophoblast (BeWo cell) spheroid attachment assay was used as an in vitro model of embryo implantation to examine the effect of testosterone on the receptivity of endometrial monolayers. Attachment of BeWo spheroids to endometrial cell monolayers was significantly reduced following pre-treatment of endometrial cells with 10nM testosterone for 24h. Flutamide (an androgen receptor antagonist, 1mM) added simultaneously with testosterone reversed the effect of treatment with testosterone alone, returning attachment rates to control levels. The transcription factor HOXA10 and the cell surface adhesion receptor aVb3 have previously been shown to play key roles in implantation. Testosterone treatment significantly decreased the expression of HOXA10 and integrin b3 in endometrial cells detected by qPCR. Immunocytochemistry showed a significant reduction in aVb3 protein expression in testosterone-treated endometrial cells.
These data suggest that the hyperandrogenism observed in women with PCOS results in reduced endometrial receptivity through the decreased expression of HOXA10 gene and aVb3 protein and this may in part be responsible for infertility in these individuals.