Atorvastatin improves ovarian function and follicular reserve in rats with premature ovarian insufficiency

Research question Can atorvastatin, with its antioxidant, anti-inflammatory and anti-apoptotic properties, improve ovarian function and follicular reserve in rats with cyclophosphamide-induced premature ovarian insufficiency (POI)? Design In this experimental study, 24 adult female Wistar rats were divided into four groups: control; POI; POI + atorvastatin; and atorvastatin. After treatment with atorvastatin, serum concentrations of total antioxidant capacity, glutathione, malondialdehyde, FSH, oestradiol, anti-M & uuml;llerian hormone, tumour necrosis factor-alpha and interleukin-6 were evaluated. Additionally, mRNA and protein expression of Bax, Bcl-2 and VEGF-A; number of follicles; and total volume of the ovary, and volumes of the cortex and medulla were examined. Results The results showed that serum concentrations of total antioxidant capacity (P < 0.001), glutathione, oestradiol and anti-M & uuml;llerian hormone (P < 0.05); mRNA and protein expression of Bcl-2 and VEGF-A (P < 0.05); number of primordial and primary follicles (P < 0.001), and preantral and antral follicles (P < 0.01); and total volume of the ovary, and volume of the cortex (P < 0.05) increased significantly in the POI + atorvastatin group compared with the POI group. Serum concentrations of malondialdehyde, FSH, tumour necrosis factor-alpha and interleukin-6; and mRNA and protein expression of Bax decreased significantly in the POI + atorvastatin group compared with the POI group (P < 0.05). Conclusions Atorvastatin reduces the detrimental effects of cyclophosphamide in the POI model significantly by reducing oxidative stress and pro-inflammatory cytokines; regulating the expression of Bax, Bcl-2 and VEGF-A; and improving ovarian function and follicular reserve.