Systematic assessment of hexavalent chromium-induced damage to male fertility and the preventive role of melatonin: a longitudinal study from the translational point of view.

Abstract

Chromium (Cr) and its compounds are closely associated with individuals' lives and extensively used in industry. Excessive exposure to hexavalent chromium (Cr(VI)) induces oxidative damage of various organs including the testes, posing a serious threat to male reproductive fitness. As an endogenous antioxidant, melatonin holds potent antioxidative and anti-inflammatory properties, becoming a potential candidate for treatment of a variety of diseases, including reproductive disorders. Here, by using a mouse model, we systematically assessed Cr(VI)-induced damage to male fertility as well as the preventive role of melatonin. We analyzed the histology and pathology of the testis and epididymis, the density, viability, and malformation of caudal epididymal sperm, the proliferative activity and apoptosis of various spermatogenic subtypes and Sertoli cells, as well as the fertility of mice at five timepoints within one cycle of spermatogenesis (Days 0, 14, 21, 28, and 35) post 14 days of Cr(VI) and/or melatonin intraperitoneal injection. We identified that the testicular damage caused by Cr(VI) persisted to Day 21 after administration and then started to be alleviated, with clear alleviation on Day 35. Pretreatment with melatonin evidently reduced Cr(VI)-induced testicular damage and accelerated spermatogenic restoration, generating an almost normal phenotype on Day 35. Melatonin pretreatment also retained the sperm quality at all time points investigated. Moreover, melatonin to some extent preserved the fertility of Cr(VI)-treated mice without apparent side effects. The findings shed light on the future clinical application of melatonin as a therapeutic agent for environmental heavy metal toxicant-induced male subfertility or infertility.