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.

Effects of Pinealectomy and Melatonin Supplementation on Elements Metabolism in Rat Testicular Tissue

“…In these limited publications, it is mostly related to zinc metabolism, which is an important trace element [12]. The relationship between melatonin and elements is either the prevention of oxidative stress caused by some toxic elements in the testicular tissue with MEL support [13] or the combined application of some antioxidant elements with MEL in the prevention of oxidative stres [11,14]. Although the effects of the pineal gland, an important neuroendocrine gland, on the male reproductive system are known, there is almost no research on how it affects the element metabolism in the testicular tissue.…”