Effects Of Resveratrol On Ovarian Development And Oocyte Apoptosis In Rats

Objective: To study the effects of resveratrol on ovarian follicle development and the mechanism of neonatal oocyte apoptosis in rats.Methods: Ovarian development of neonatal rats which were treated with resveratrol (20mg/kg/d) by intraperitoneal injection on day 1-4, or whose mothers were treated with resveratrol (20mg/kg/d) on day 10.5 after detected vaginal plug till delivery by intragastric administration and 11-15-month-old rats which were treated with resveratrol (20mg/kg/d) by intragastric administration for 16 weeks were investigated by hematoxylin-eosin staining. The oocyte apoptosis profiles in neonatal rats were determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) staining. The expression of Forkhead box group O (Foxo3a), Bim and p27KIP1 were detected by immunohistochemistry staining. The estrous cycle patterns were determined by daily observations of vaginal smears for 16 weeks in 11-15-month-old rats.Results: (1) The percentage of unassembled follicles and the total number of oocytes increased in the PD1 and PD2 rat ovaries which were intraperitoneally (ip) injected with resveratrol (20 mg/kg/day) or whose mothers were treated with resveratrol (20 mg/kg/day) by intragastric administration from the day 11 after the detection of vaginal plug till delivery. In PD 4 rat ovaries, the total number of oocytes was significantly increased in the groups treated with reveratrol. Moreover, more unassembled follicles and lesser primary follicles were existed in the groups treated with reveratrol than that of controls; (2) In the 15-month-old rat ovaries, the resting follicles and the total oocytes increased, while the developing follicles and atretic follicles decreased after resveratrol treatment. (3) The percentage of TUNEL positive oocytes decreased in PD1 and PD2 rat ovaries after resveratrol treatment, and the positive rate of Foxo3a, Bim and p27KIP1 in oocytes from PD 2 rat ovaries was lower in resveratrol treatment group than in controls. (4) 11-15-month-old rats treated with resveratrol maintained regular estrous cycles. Conclusions: Resveratrol may delay oocyte nest breakdown, inhibit the primordial to developing follicle transition, extend the entire growth phase of a follicle, reduce dominant follicle numbers per cycle to increase the reserve of germ cells, decrease follicles atresia during rat ovarian development from birth to early old age, and retard climacterium in rats. The signaling pathways of SCF-PI3K/Akt-Foxo3a- Bcl-2 family members (Bim, Bax and Bad)/p27KIP1 may be the main anti-apoptotic signal pathways in resveratrol-treated neonatal rat ovaries. Our results suggest that resveratrol may have a great health benefit to ovarian development and ovarian lifespan.