Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

Abstract

ObjectiveVery little information is known about the toxic effects of cadmium on somatic cells in mammalian testis. The objective of this study is to explore the toxicity of cadmium on piglet Sertoli cells.MethodsSertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet Sertoli cells were identified by oil red O staining and Fas ligand (FasL) expression as assayed by immunocytochemistry and expression of transferrin and androgen binding protein by RT-PCR. Sertoli cells were cultured in DMEM/F12 supplemented with 10% fetal calf serum in the absence or presence of various concentrations of cadmium chloride, or treatment with p38 MAPK inhibitor SB202190 and with cadmium chloride exposure. Apoptotic cells in seminiferous tubules of piglets were also performed using TUNEL assay in vivo.ResultsCadmium chloride inhibited the proliferation of Piglet Sertoli cells as shown by MTT assay, and it increased malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) activity. Inhibitor SB202190 alleviated the proliferation inhibition of cadmium on piglet Sertoli cells. Comet assay revealed that cadmium chloride caused DNA damage of Piglet Sertoli cells and resulted in cell apoptosis as assayed by flow cytometry. The in vivo study confirmed that cadmium induced cell apoptosis in seminiferous tubules of piglets. Transmission electronic microscopy showed abnormal and apoptotic ultrastructure in Piglet Sertoli cells treated with cadmium chloride compared to the control.Conclusioncadmium has obvious adverse effects on the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis, and aberrant morphology. This study thus offers novel insights into the toxicology of cadmium on male reproduction.

Comparison of Ferulic Acid and Sildenafil, Therapeutic Role against Testicular Injury Induced by Cadmium Chloride in Adult Male Albino Rat

“…These results might be due to direct inhibitory effect of cadmium on production of inhibin-B from sertoli cell. This is in agreement with results of [34]. However, it was found in the present study thattoxic effect caused by cadmium was ameliorated with ferulic acid and sildenafil , where the tissue inhibin-Blevel was restored and elevated.whileT3&T4 level was decreased.…”

Extracellular-Superoxide Dismutase Expression in COS7 Cells Exposed to Cadmium Chloride

“…[1][2][3] It has been well recognized that Cd-related cytotoxicity is closely associated with oxidative stress, which is induced by the generation of ROS and the disturbance of anti-oxidative enzymes, such as catalase and GSH-Px 19) ; however, the effect of Cd exposure on the expression of EC-SOD and other SODs has not been elucidated. In this study, we demonstrate for the first time that EC-SOD was decreased by CdCl 2 exposure through intracellular ROS accumulation and the p38-MAPK pathway in COS7 cells.…”

“…It has been reported that Cd negatively regulates several anti-oxidative enzymes, including catalase and GSH-Px in piglet Sertoli cells and hepatocytes 19) ; however, the regulation of SODs by Cd exposure is still unknown. Exposure to CdCl 2 significantly decreased the expression of EC-SOD in a dose-dependent manner (Fig.…”

“…19) Further, we have reported that hypoxia (1% O 2 ) and hypoxia mimetic, cobalt chloride (CoCl 2 ), decreased the expression of EC-SOD through intracellular ROS generation and mitogen-activated protein kinase (MAPK) activation in green monkey renal tubule epithelial cells (COS7 cells) 20) ; however, the regulation of EC-SOD by Cd exposure remains unclear. In order to address these issues, we investigated the effect of CdCl 2 exposure on the expression of SODs in COS7 cells.…”

Cell‐specific ablation in the testis: what have we learned?

“…2). This also does not meet all the criteria of the ideal cell ablation method as the impact of cadmium is not restricted to one testicular cell type (Marettova et al ., 2015) but the Sertoli cells appear to be the most vulnerable to cadmium exposure and even low doses have specific effects on the Sertoli cells (vacuolisation, cell contraction, detachment, inhibition of protein synthesis, apoptosis) (Clough et al ., 1990; Zhang et al ., 2010). Given its effect on the Sertoli cells, cadmium has been used to explore the role of the Sertoli cells in development of the spermatogonial stem cell niche.…”