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

摘要

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 E 2 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.