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.

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

Vol 98, Issue 5, Pages 1283-1290



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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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.