| Impact of Metformin as mTOR/S6K1–4EBP1 inhibitor in Premature Ovarian Insufficiency |
| Paper ID : 1116-ISCH |
| Authors |
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Mira Latif Sabry * Teaching Assistant Pharmacology and Toxicology Department, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University |
| Abstract |
| Premature ovarian insufficiency (POI) is a major adverse effect of cyclophosphamide (CYC), a widely used chemotherapeutic agent. Its mechanism is strongly linked to accelerated follicular activation and depletion of the ovarian reserve through hyperactivation of the mTOR/S6K1–4EBP1 pathway. This study aimed to evaluate the protective effect of Metformin, an mTOR inhibitor, on CYC-induced ovarian damage and its impact on fertility preservation. Forty-five female rats were allocated into three groups: Control, CYC, and CYC+Metformin. CYC was administered for 15 days, followed by 15 days of Metformin treatment. Hormonal levels (FSH, LH, E2, AMH) were measured by ELISA; ovarian morphology and follicular changes were examined via H&E staining; protein expression of FOXO3a, mTOR, YAP, and TAZ was assessed by western blot; and apoptosis was evaluated through caspase-3 immunohistochemistry. CYC exposure resulted in reduced ovarian weight, disrupted hormone balance, increased apoptosis, and impaired fertility. Metformin significantly counteracted these effects by restoring hormone levels, improving ovarian histology, reducing apoptosis, and enhancing fertility outcomes. These findings highlight Metformin’s protective potential in preserving ovarian reserve and function during chemotherapy. Targeting the mTOR/S6K1–4EBP1 pathway with Metformin may represent a promising strategy for fertility preservation in patients at risk of chemotherapy-induced POI. |
| Keywords |
| Premature Ovarian Insufficiency, Metformin, mTOR/S6K1–4EBP1 pathway ,Fertility preservation. |
| Status: Abstract Accepted (Poster Presentation) |