Role of autophagy in cadmium-induced testicular injury

Abstract

<jats:p> The testis is sensitive to cadmium, but studies investigating cadmium-induced testicular injury have not yet clearly revealed the underlying mechanisms. This study aimed to investigate the injurious effects of cadmium on rat testes and the role that autophagy plays in this process. Wistar rats were randomly divided into four groups and intraperitoneally injected with 0.2 (low), 0.4 (middle), and 0.8 mg/kg·body weight (high) cadmium chloride for 5 weeks, while the control rats were injected with equal volume of saline. Rats exposed to cadmium appeared inactive and had reduced body weights and increased testicular organ coefficients at the end of treatment compared with control rats. Atomic absorption results showed that cadmium levels increased with increased cadmium exposure. Hematoxylin and eosin staining of testicular sections showed seminiferous tubular atrophy, decreased pipe diameter, spermatogonial stem cells falling off the inner lining, and reduced germ cell layers of disorderly arrangements in cadmium-treated rats. Immunohistochemical and western blot results both showed that levels of the autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3B) increased with increased cadmium exposure. We also found that LC3B-II and calcium-sensing receptor (CSR) levels in cadmium-exposed rats significantly increased. By immunofluorescence, we found that the percentage of cells that expressed the CSR was significantly higher in LC3B-positive than LC3B-negative cells. Together, our results showed that cadmium accumulates in the testes causing testicular injury, which may be related to increased autophagy levels. Furthermore, calcium disorders associated with the CSR may reveal a potential way to activate autophagy. </jats:p>

Reproductive effects of cadmium on sperm function and early embryonic development in vitro

“…Cadmium has been demonstrated to impair mammalian reproduction in recent studies. Destruction of testis caused by Cd 2+ has been carefully studied [ 14 – 17 ]. However, the sperm are another key cell type affected by Cd 2+ , and given their critical role in male reproduction, the deleterious effects of Cd 2+ exposure are of great clinical importance.…”

Antagonistic effects of lycopene on cadmium-induced hippocampal dysfunctions in autophagy, calcium homeostatis and redox

“…Autophagy has been determined necessary for Cd-induced hepatotoxicity, testicular injury and toxicity in mesenchymal stem cells [ 41 – 43 ]. There is also mounting evidence implicating autophagic dysfunction in the pathogenesis of several major neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease and Huntington's disease [ 3 ].…”

Nitrobenzene-induced hormonal disruption, alteration of steroidogenic pathway, and oxidative damage in rat: protective effects of Vernonia amygdalina

“…Chemically induced endocrine disruption and testicular damage may occur after administration of toxicants or potentially toxic drugs. The clinical symptoms of chemicallyinduced testicular disorder includes abnormalities in the testicular structure and alteration in its physiological functions [5,6]. A group of xenobiotics known as endocrine disruptors may alter the physiological activities of biological systems, mediate hormonal balance, and/or adversely influence biological functions and activities of organs that hormones control or modulate, especially in reproductive systems [7].…”