Neonatal exposure to estradiol valerate reprograms the rat ovary androgen receptor and anti-Müllerian hormone to a polycystic ovary phenotype

Abstract

To understand the impact of exposure to steroids in the early step of ovary development(a stage occurring in uterus in humans), we studied neonatal exposure to estradiol valerate (EV) in rats regarding polycystic ovary (PCO) development as well as expression of androgen receptor (Ar) and anti-Müllerian hormone (AMH), a marker of ovarian follicular development. Rats exposed to one dose of EV (10 mg/kg, sc) during their first 12 h of life were euthanized at 2, 30 and 60 days of age. Gene array and real-time PCR studies showed Ar and AMH up regulation in the ovary at 2 days of age and persisted at 60 days of age, when a PCO phenotype was evident with increased levels of Ar and AMH proteins. The single neonatal exposure in rats suggests participation of EV in developing PCO syndrome. Its persistence also suggests that estradiol reprograms ovarian function and disease during adulthood.