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

Capsule:
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.

Authors:
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

Abstract:

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

Design:
Basic experimental study.

Setting:
University animal laboratory.

Animals:
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.

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

Results:
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.

Conclusion:
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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