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

• Published in: Reproductive biomedicine online 2024-11, Vol.49 (5), p.104324, Article 104324
• Main Authors: Notghi, Parmis, Mehranjani, Malek Soleimani, Shariatzadeh, Seyed Mohammad Ali
• Format: Article
• Language: English
• Subjects: Apoptosis; Atorvastatin; Inflammation; Oxidative stress; Premature ovarian insufficiency; VEGF-A
• ISSN: 1472-6483; 1472-6491; 1472-6491
• DOI: 10.1016/j.rbmo.2024.104324

•Premature ovarian insufficiency (POI) was induced in rats with cyclophosphamide.•Atorvastatin reduces oxidative stress, inflammation and apoptosis in the POI model.•Atorvastatin ameliorates ovarian structure and function in the POI model.•Atorvastatin causes follicular survival in the POI model. 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)? 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-Müllerian 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. The results showed that serum concentrations of total antioxidant capacity (P < 0.001), glutathione, oestradiol and anti-Müllerian 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). 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.