Maternal testosterone excess contributes to reproductive system dysfunction of female offspring mice.

Abstract

Hyperandrogenism is considered as one of the most important characteristics of polycystic ovary syndrome (PCOS) which affects more than 10% percent of females in reproductive age and is a common cause of infertility. In addition to the impacts on patients themselves, maternal androgen excess has also been reported to impair the growth and development of offspring. In our current study, we found that maternal testosterone (T) treatment during different gestational stages increased the percentage of atretic follicle and decreased the corpus luteum formation in female offspring. In addition, decreased serum estradiol (E2) level and increased T level were also observed in female offspring of T treated mice during late gestational stage. Further studies revealed that Forkhead box protein L2 (FOXL2) and Cytochrome P450 family 19 subfamily a member 1 (CYP19A1) expression in granulosa cell of these female offspring mice were decreased. By using mouse primary granulosa cell and KGN cell line, we demonstrated that declined FOXL2 and CYP19A1 in ovarian granulosa cell partially may contributes to disturbed sex hormone synthesis in female offspring of testosterone treated mice during late gestational stage. Findings from our current study highlight a critical role of excess maternal T exposure, especially during late gestational stage, which could further lead to aberrant ovary development and sex hormone synthesis in female offspring.