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

We describe the existence of a specific postnatal window of vulnerability during which estradiol valerate exposure irreversibly programs changes in the follicular development, ovulation, and cyclic estrual activity of rats.

Gonzalo Cruz, Ph.D., Rafael Barra, Ph.D., Daniel González, D.V.M., Ramón Sotomayor-Zárate, Ph.D., Hernán E. Lara, Ph.D.

Volume 98, Issue 5, Pages 1283-1290, November 2012


To investigate the developmental window in which estradiol exposure produces irreversible changes in ovarian function resulting in polycystic ovary.

Basic experimental study.

University animal laboratory.

Thirty Sprague-Dawley rats were administered a single EV dose (10 mg/Kg of weight) at 1, 7, 14, 21 or30 days of age. Control rats were injected with the vehicle at 1 day of age. All rats were sacrificed at 6 months of age.

Observation of vaginal opening, estrous cyclicity by vaginal smears, and ovarian morphometry in the 6-month-old rat.

Rats exposed to estradiol at 1, 7 or 14 days of life did not show estrual cycling activity and maintained a PCO condition throughout the entirety of the study. However, if the exposure to estradiol occurred after postnatal day 21, the PCO-induced condition was reversible. In rats that developed a permanent PCO condition we observed significant effects of estradiol 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.

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.

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