Protective Effect of Grape Seed Extract on Sperm DNA Integrity and Early Embryonic Development in Male Balb/c Mice Treated with Fluoxetine

Background: Fluoxetine (FLX), an antidepressant, has toxic effects on embryonic stem cell differentiation and fertility. Objectives: The aim of this study was to investigate the effect of grape seed extract (GSE) on sperm DNA integrity and early embryonic development in Balb/c mice exposed to FLX. Methods: In this study, 32 male Balb/c mice (6 - 8 WK, 30 ± 2 g) were utilized and randomly divided into four groups: Control, FLX (40 mg/kg B.W), FLX (40 mg/kg B.W) + GSE (150 mg/kg B.W), and GSE (150 mg/kg B.W). In all groups, the caudal epididymis was collected on day 42. Superovulation was induced in adult female mice, and fertilized oocytes were assessed. The amount of two-cell embryos was checked after 24 days of cell culture, and at 96 hours after fertilization, blastocysts and hatched embryos were examined. Results: The results indicated a significant increase in the percentage of sperm with DNA damage (P = 0.04) and immature sperm in the FLX group (P = 0.02), along with a significant reduction in the percentage of zygotes (P = 0.25), blastocysts (P = 0.01), and hatching embryos (P = 0.03). However, the FLX + GSE group exhibited a remarkable improvement in all of the aforementioned parameters and in reducing embryo toxicity. The percentage of two-cell embryos did not differ significantly between the groups. Conclusions: This study demonstrated the antioxidant activity of GSE in mitigating FLX-induced embryo toxicity.