Toxicological outcome of phthalate exposure on male fertility: Ameliorative impacts of the co-administration of N-acetylcysteine and zinc sulfate in rats

Abstract

Background: Reports have shown that humans are consistently exposed to environmental toxicants such as phthalate (PHT) during their daily activities. This results in reproductive dysfunction and infertility-related issues as already noted in human and experimental animals. We therefore designed this study to investigate fertility outcome in phthalate-exposed male rats treated with N-acetylcysteine (NAC) and zinc sulfate (ZnSO4) with the view of providing a therapeutic alternative to reproductive toxicity caused by phthalate. The research was done in two phases. In phase 1, thirty-five male Wistar rats were randomly assigned to one of five (n = 7) groups given the following treatments for 21 days: group A was given distilled water as a control, while groups B, C, D, and E were given phthalate (750 mg/kg/day). Animals in groups C to E were also given ZnSO4 (0.5 mg/kg/day), N-acetylcysteine (100 mg/kg/day), and ZnSO4 (0.5 mg/kg/day) + N-acetylcysteine (100 mg/kg/day) in addition to phthalate. In phase 2, animals from groups in phase 1 were mated with females for fecundity testing. Results: The result shows alteration in testicular and epididymis weight and testis/epididymis ratio, semen parameters, sperm capacitation and acrosome reaction, sperm DNA, serum Zn and Mg, testicular mitochondria apoptosis mechanisms (TNF-α and BCL-2), and testicular Ca2+-ATPase as well as fecundity outcome in the phthalate-treated group. However, ZnSO4 and NAC successfully ameliorated the deleterious effects of phthalate on semen parameters, sperm capacitation and acrosome reaction, serum electrolyte and mitochondria apoptosis mechanisms, and testicular electrogenic Ca2+-ATPase in phthalate-induced male rats with a better outcome in the combined therapy. Pregnancy outcome and litter sizes were also higher in the combined therapy when also compared with the phthalate-treated groups. Conclusion: According to the result, ZnSO4 and NAC increased fertility outcome in phthalate-treated male rats through enhancement of testicular BCL-2, serum electrolyte, testicular Ca2+ATPase pumps, and cytoprotection.