Mifepristone (RU486) Induces Polycystic Ovarian Syndrome in Female Wistar Rats with Features Analogous to Humans

Abstract

Numerous inducers of polycystic ovarian syndrome (PCOS) at different doses have been proposed in several experimental animals but there is no consensus on an appropriate dose(s) that should ideally reproduce the key biochemical and clinical features of PCOS similar to those of humans. Therefore, this study was aimed at investigating an appropriate dose(s) for the induction of PCOS in female Wistar rats. Twenty-four female albino rats (190.00 ± 13.00 g) with 4-5 days of estrus cyclicity were completely randomized into 4 groups (A - D) of six animals each. Animals in group A (control) were subcutaneously administered 0.2 ml of pure olive oil, while those in groups B, C and D were subcutaneously administered same volume corresponding to 5.0, 7.5 and 10.0 mg of mifepristone in olive oil for 9 days starting from the day of estrus (Day 1). The estrus cycle, serum testosterone (T), estradiol (E), prolactin (Pr), follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), insulin (Is), weight of the animals, fasting blood glucose (FBS) and ovarian morphology were monitored/evaluated/examined. The 5.0 mg of mifepristone extended the estrus stage for four days, increased (p<0.05) the levels of serum E, P, Pr, FSH, T, triacylglycerides (TAG), and total cholesterol (TC) as well as decreased the concentrations of LH and high density lipoprotein-cholesterol (HDL-C). There was no significant difference (p<0.05) in the Is concentration, animal body weights and FBS at day 10 in rats administered 5.0 mg of mifepristone. The 7.5 mg of mifepristone produced irregular estrus cycle, increased Pr, TAG, T, and TC concentrations and FBS whereas it decreased E, P, HDL-C, and LH. The Is, FSH and body weights of the animals were not significantly altered at 7.5 mg of mifepristone. The 10.0 mg of mifepristone produced irregular estrus cycle, increased the levels of E, TAG, Is, LH, T as well as decreased the levels of P and HDL-C. The levels of Pr, FSH, TC, body weights and FBS were not significantly altered at this dose. There was no ovarian follicular growth and atresia in the 5.0 and 7.5 mg mifepristone-treated rats whereas the 10 mg of mifepristone produced these histopathological features. Overall, the study concluded that subcutaneous administration of mifepristone (RU486) induces polycystic ovarian syndrome in rats through deprivation of progesterone with the 10 mg producing majority of the key biochemical and clinical features associated with PCOS in humans. The study, therefore, recommends the subcutaneous administration of mifepristone (RU486) on daily basis for 9 days as a good model for inducing PCOS in animals.