The Possible Protective Effect of Vitamin E and Melatonin on Cyclophosphamide-Induced Ovarian Failure in Adult Female C57BL/6 Mice: Histological and Immunohistochemical Study

Background: Cyclophosphamide has a toxic effect on the ovaries and may induce ovarian failure. Premature ovarian failure (POF) is a common condition that stands for cessation of the ovarian functions in women before the age of 40 years. Vitamin E shows antioxidant features that can protect ovary from toxicity of cyclophosphamide. Melatonin is known for having antioxidant features that help ovary to restore its normal structure. Purpose: Study the potential protective role of co-administration of vitamin E and melatonin on the ovarian structure in cyclophosphamide induced ovarian failure. Materials and Methods: The mice were divided into 5 groups (group I: control group that received orally distilled water and olive oil. group II: cyclophosphamide group (75 mg/kg/day, intraperitoneally), group III: cyclophosphamide+ vitamin E group (200 mg/kg/day, by orogastric tube), group IV: cyclophosphamide+ melatonin group (50 mg/kg/day, by orogastric tube), group V: cyclophosphamide+ vitamin E+ melatonin group. The ovarian sections were examined histologically and immunohistochemically. Results: Ovaries of cyclophosphamide+ vitamin E group and cyclophosphamide+ melatonin group had partial improvement in the ovarian structure with reappearance of follicles at different stages of development, partial regression in the extent of cortical fibrosis and moderate decrease in immunohistochemical reaction against caspase-3 compared to cyclophosphamide group. Ovaries of cyclophosphamide+ vitamin E+ melatonin group showed restoration of nearly normal structure with normal appearance of follicles, zona pellucida and minimal cortical collagen deposition. Morphometric studies of the cyclophosphamide+ vitamin E+ melatonin group revealed a marked increase in follicle count, diameter and ovarian diameter with a decrease in collagen fibers deposition. Conclusion: A Combination of vitamin E and melatonin with cyclophosphamide helps to preserve the ovary and restore normal ovarian structure in comparison to the use of vitamin E or melatonin alone. KEY WORDS: C57BL/6 mice - caspase reaction - cyclophosphamide - follicles -melatonin - morphometric - premature ovarian failure – vitamin E.