Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats

Objective: To investigate the developmental window in which E-2 exposure produces irreversible changes in ovarian function resulting in polycystic ovary. Design: Basic experimental study. Setting: University animal laboratory. Animal(s): Thirty Sprague-Dawley rats were administered a single E-2 valerate dose (10 mg/kg of weight) at 1, 7, 14, 21, or 30 days of age. Control rats were injected with the vehicle at 1 day of age. All rats were sacrificed at 6 months of age. Intervention(s): Observation of vaginal opening, estrous cyclicity by vaginal smears, and ovarian morphometry in the 6-month-old rat. Main Outcome Measure(s): Measurement of ovarian noradrenaline by high-performance liquid chromatography coupled with electrochemical detection, serum levels of LH by enzyme-linked immunoassay, P, androstenedione, and E2 by enzyme immunoassay. Result(s): Rats exposed to E-2 at 1, 7, or 14 days of life did not show estrual cycling activity and maintained a polycystic ovary (PCO) condition throughout the entirety of the study. However, if the exposure to E-2 occurred after postnatal day 21, the PCO-induced condition was reversible. In rats that developed a permanent PCO condition, we observed significant effects of E-2 on ovarian morphology if exposure occurred on postnatal day 1 and a presumable effect on the hypothalamus if the exposure occurred between postnatal days 1 and 14. Conclusion(s): Our findings suggest that in rats, the most sensitive period for the promotion of an irreversible PCO morphology by estrogenic compounds is during neonatal early follicular development. (Fertil Steril (R) 2012;98:1283-90. (C)2012 by American Society for Reproductive Medicine.)