Effective attenuation of glyphosate-induced oxidative stress and granulosa cell apoptosis by vitamins C and E in caprines

Pesticides are known to cause a wide range of reproductive problems that possess degenerative effects on mammalian fertility. Glyphosate (GLP), a broad-spectrum organophosphate herbicide, is known to be a potent mammalian toxicant. The present study aims at assessing the GLP-induced (0.1, 2.0, and 4.0 mg/ml) granulosa cells toxicity and evaluating the mitigating effects of vitamins C and E (0.5 mM and 1.0 mM) in healthy caprine antral follicles, cultured in vitro in a dose- and time-dependent manner (24, 48, and 72 hr) and subjected to various cytotoxic and geno-toxic analysis, namely, classic histology, EB/AO differential staining, oxidative stress parameters, and antioxidant enzymatic activity. The histomorphological analysis and EB/AO staining elucidated increase in the incidence of apoptotic attributes within granulosa cells with increasing dose and duration of the GLP treatment. The highest apoptotic frequency was observed at 4.0 mg/ml GLP after 72-hr exposure duration in comparison with the control. GLP exposure also led to a significant decline in the antioxidant enzymes' activity, namely, SOD, catalase, and GST along with enhanced lipid peroxidation and reduced FRAP activity in a dose- and time-dependent manner. Vitamins C and E supplementation decreased oxidative stress-mediated granulosa cells apoptosis, suggesting its efficiency to diminish GLP-mediated GCs cytotoxicity and thereby, preventing associated fertility disorders.