Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

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.

Preliminary study of the ameliorative effects of melatonin on cadmium‐induced morphological and biochemical alterations in the rat Harderian gland

“…It is well known that Cadmium (Cd), a heavy metal, has been associated both with oxidative stress and autophagy (Gunnarsson et al, 2004; Stoica et al, 2000), in addition, it is proposed to be one of the environmental endocrine disruptors altering testosterone and estradiol (E 2 ) productions throughs the inhibition of the activity of steroidogenic enzymes (Ciarrocca et al, 2013). In fact, Cd can directly bind to estrogen and androgen receptors (Gunnarsson et al, 2007; Stoica et al, 2000) or alter the expression of enzymes related to steroidogenesis, such as StAR, 3β‐hydroxisteroid dehydrogenase 3β‐HSD (Venditti et al, 2021a), however, the mechanisms underlying the anti‐steroidogenic consequence persist largely unexplored. For all these characteristics we decided to use Cd just to induce oxidative stress in the rat HG in ex vivo experiments.…”

Effects of Cadmium Exposure on Leydig Cells and Blood Vessels in Mouse Testis

“…In our study, significantly weaker staining of 3β-HSD activity was detected in the high-dose (2.5 mg/kg) group, but both the 0.5 and 1.5 mg/kg CdCl 2 treatments also exhibited inhibitory effects on 3β-HSD activity. In addition, previous studies have shown that 3β-HSD activity or expression is downregulated by Cd treatment [47,50]. Treatment with Cd also causes a significant decrease in serum testosterone levels [51].…”

Antioxidant Paradox in Male Infertility: ‘A Blind Eye’ on Inflammation

“…Aside from that, it has been demonstrated that overly high quantities of antioxidants are teratogenic to embryos [ 56 ]. On the contrary, there has been research demonstrating that antioxidant therapy can help to improve male reproductive health [ 5 , 32 , 57 , 58 , 59 , 60 , 61 ]. In the current state of reproductive medicine research, antioxidant treatment for male infertility has received considerable attention ( Table 1 ).…”