HOXA10 expression is decreased by testosterone in luteinized granulosa cells in vitro

: Polycystic ovary syndrome (PCOS) is perhaps the most prevalent endocrine disorder in women of reproductive age, characterized by elevated levels of circulating androgens or clinical manifestations of androgen excess. The specific cytokine profile of PCOS patients is probably related to the lower implantation rate, since follicular fluid appears to function as an embryotrophic agent. For a better understanding of the local regulation of human follicles, the present study investigated the protein expression levels and cellular localization of HOXA10 in granulosa cells (GCs) from women with normal ovarian function undergoing IVF due to their husbands suffering from azoospermia. We demonstrated by immunohistochemical studies that the expression of HOXA10 was mainly localized in the cytoplasm of GCs. Our data indicate that these alterations were associated with changes in the expression of ovarian transcription factors of HOXA10. GC dose-responsive decreases in HOXA10 protein were observed in response to physiological or supraphysiological concentrations (10-4 to 10-7 M) of testosterone. These data reveal that testosterone may be involved in HOXA10 gene regulation in GCs. Decreased HOXA10 expression in GCs treated with testosterone suggest that this androgen is responsible for the decreased expression of HOXA10 in PCOS patients.