[Study on the oxidative stress in the ovaries of a rat model of polycystic ovary].
OBJECTIVE
To establish a pathological animal model of polycystic ovary (PCO) by letrozole in rats. Investigate whether PCO were mediated by the effect of oxidative stress by measuring oxidative stress levels in this cohort of rats with PCO, and proceed a new way of treatment for polycystic ovary syndrom (PCOS).


METHODS
90 SD female rats aged 6 weeks were randomly divided into two groups, including a control group of 45 rats that received vehicle only [19% aqueous solution of carboxmethlycellulose (CMC), 1 mL/d] once daily orally (p.o.), and an experimental group of 45 rats, which were administered letrozole at concentrations of 1 mg/kg p.o. dissolved in 1% CMC (1 mL/d) once daily. The treatment period was 28 d. During this period, vaginal smears were collected daily for estrus cycle determination and body masses were measured every 7 d. On the day subsequent to the last letrozole dose administration, rats were killed; Uteri and ovaries were then excised and weighed for the calculation of organ indexes. Serum hormone levels, SHBG and histologic changes in the ovaries were examined. Then testosterone free index (FAD) was calculated. Oxidant status was evaluated by determination of ovarian total oxidant status (TOS), malondialdehyde (MDA) concentration and intracellular reactive oxygen species (ROS) level, while antioxidant status was evaluated by determination of total antioxidant status (TAS) and superoxide dismutase (SOD) concentration.


RESULTS
Vaginal smear test showed the estrus cycle began to disappear from day 12 to day 15. A statistically significant difference in growth curves, ovarian weights, uterine weights and organ indexes between the groups were also observed. In rats with PCO serum testosterone (T), follicle-stimulating hormone (FSH) concentrations and free androgen index (FADI) were significantly increased compared with the control group (rats without PCO). However, rats with PCO had decreased levels of estrogen (E2), luteinizing hormone (LH), and progesterone (P) compared with the control group. In a rat model of PCO achieved via letrozole, it was found that the levels of TOS, MDA, oxidative stress index (OSI) and intracellular ROS were significantly increased, while the TAS level, SOD content were significantly decreased in the ovary homogenates (P<0.05). The results indicated that the PCOS pathological process significantly increased the oxidative stress production.


CONCLUSIONS
PCO rat model successfully induced via letrozole, and it is a suitable model for study of ovarian lesions. Oxidative stress also contributes to the PCO rat model, the protective effect of antioxidant might provide a new insight into the potential therapeutic solution to PCOS.
Jin
J
Gong
Dong-bo
DB
Wu
Lan-lan
LL
Zhang
Jia
J
Li
Xing
X
Zhao
Dan
D
Zhang
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D000077289:Letrozole; D007986:Luteinizing Hormone / Q000097:blood; D008315:Malondialdehyde / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010053:Ovary / Q000503:physiopathology*; D018384:Oxidative Stress; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000494:pharmacology
D000975:Antioxidants; D004967:Estrogens; D009570:Nitriles; D017382:Reactive Oxygen Species; D014230:Triazoles; D013739:Testosterone; D011374:Progesterone; D008315:Malondialdehyde; D000077289:Letrozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone