Coumarin attenuates cyclophosphamide-induced premature ovarian failure in mice by suppressing oxidative stress and apoptosis

Abstract

Cyclophosphamide (CTX) is a chemotherapy alkylating agent that causes many side effects, including the occurrence of Premature ovarian failure (POF). The present study aims to investigate the effects of coumarin (COU), as an antioxidant, on apoptosis and oxidative stress in the CTX-induced POF mouse model. NMRI female mice were randomly divided into four groups: 1- The control group received 200 mg/kg normal saline every two days for 6 days. 2- The POF group was administered three 200 mg/kg doses of CTX every two days. 3- The COU group received 40 mg/kg of coumarin for 14 days. 4- The POF+COU group received 40 mg/kg coumarin for 7 days before and after the induction of the POF mouse model. Vaginal smears, weighing, hormonal, histological, and biochemical factors, as well as the expression of apoptosis genes, were evaluated after inducing the POF model. Coumarin effectively reduced estrous cycle disorders, leading to a more regular cycling pattern. COU increased both ovarian and body weight, and improved hormone levels. Ovarian reserve and antral follicles in the POF+COU group increased significantly compared to the POF group. Compared to the POF group, the POF+COU group showed a significant decrease in ROS and a significant increase in antioxidant enzymes. COU-treated groups showed a significant reduction in the expression of Caspase-8 and Caspase-9 genes and the apoptosis index compared to the POF group. As a plant antioxidant, coumarin could improve ovarian function and reduce apoptosis and oxidative stress in the POF mouse model.