Neonatal exposure to 17α-ethynyl estradiol affects ovarian gene expression and disrupts reproductive cycles in female rats

•Neonatal exposure to ethynyl estradiol (EE) induced delayed reproductive dysfunction.•Ectopic expression of LHCGR was observed in ovaries from EE-treated animal.•The expression of LHCGR was directly induced by EE treatment in vitro.•We propose that LHCGR might provide a marker gene for screening EDCs.

Neonatal exposure to synthetic estrogen causes delayed reproductive dysfunction in female rats. Exposure to 17α-ethynyl estradiol (EE, low: 20 and high: 2000 μg/kg) induced an abnormal estrous cycle during PND171-190 in low-dose and PND126-145 in high-dose group. At PND90 within normal estrous cycle, high-dose animals showed lack of LH surge and low of ovarian hormones in serum level. Gene expression analysis demonstrated that level of mRNA encoding luteinizing hormone/chorionic gonadotropin receptor (LHCGR) was higher in EE-treated ovaries than in control ovaries, and LHCGR protein colocalized with apoptosis-related proteins in the interstitial area of the ovary. At PND1, ovarian LHCGR mRNA levels were higher in EE-treated rats than in control rats, and direct induction of LHCGR expression by EE was observed in vitro. Our results indicate that neonatal exposure to EE induces irregular LHCGR expression in the immature ovary, which may influence the occurrence of delayed reproductive dysfunction in adult animals.