Abstract
Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues, including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells and provoked testicular injury, as documented by biomolecular and histological alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration produces affects in mitigating Cd-induced toxicity on adult rat testis, as demonstrated by the reduction of oxidative stress and apoptosis, with reversal of the observed histological changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, which are involved in the germ cells’ differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT attenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity by acting on DAAM1 and PREP expression, encouraging further studies to prove its effectiveness in human health.
Highlights
Reproduction is an essential biological feature that increases the number of living beings and is necessary for the survival and the evolutionary continuity of the species.For this, the production and differentiation of good quality gametes is a fundamental for reproductive success
The control and MLT-treated rats presented a regular seminiferous epithelium and interstitial compartment characterized by the presence of germ cells (GC) in all the different stages of differentiation, with the tubular lumina being filled with mature SPZ and by the Leydig cells (LC) and normal blood vessels in the interstitium
The histological data were confirmed by the analysis of three morphometric parameters (Table 1), which showed that the tubules diameter (p < 0.001), the epithelium thickness (p < 0.001), and the percentage of tubular lumina occupied by SPZ (p < 0.001) were significantly lower in Cd-treated group as compared to the control and MLT groups
Summary
Reproduction is an essential biological feature that increases the number of living beings and is necessary for the survival and the evolutionary continuity of the species.For this, the production and differentiation of good quality gametes is a fundamental for reproductive success. Many reports demonstrated that Cd affects animal and human spermatogenesis, acting at different levels: disturbing the hypothalamus-pituitary-testis (HPT) axis; altering seminiferous tubules, blood-testis barrier, and testicular endothelium; and resulting in reduced spermatozoa (SPZ) quantity and quality [7,8]. All the above-mentioned effects of Cd on the testis have been related, at the cellular and molecular level, to an increase of oxidative stress, augmented tissue apoptosis and necrosis, and alteration of steroidogenesis and spermatogenesis; all the combined effects result in the reduction of normal SPZ morphology and motility and, lead to reproductive disorders [9,10,11]
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