Hexavalent chromium induces apoptosis in male somatic and spermatogonial stem cells via redox imbalance.
Hexavalent chromium [Cr(VI)], an environmental toxicant, causes severe male reproductive abnormalities. However, the actual mechanisms of toxicity are not clearly understood and have not been studied in detail. The present in vitro study aimed to investigate the mechanism of reproductive toxicity of Cr(VI) in male somatic cells (mouse TM3 Leydig cells and TM4 Sertoli cells) and spermatogonial stem cells (SSCs) because damage to or dysfunction of these cells can directly affect spermatogenesis, resulting in male infertility. Cr(VI) by inducing oxidative stress was cytotoxic to both male somatic cells and SSCs in a dose-dependent manner, and induced mitochondria-dependent apoptosis. Although the mechanism of Cr(VI)-induced cytotoxicity was similar in both somatic cells, the differences in sensitivity of TM3 and TM4 cells to Cr(VI) could be attributed, at least in part, to cell-specific regulation of P-AKT1, P-ERK1/2, and P-P53 proteins. Cr(VI) affected the differentiation and self-renewal mechanisms of SSCs, disrupted steroidogenesis in TM3 cells, while in TM4 cells, the expression of tight junction signaling and cell receptor molecules was affected as well as the secretory functions were impaired. In conclusion, our results show that Cr(VI) is cytotoxic and impairs the physiological functions of male somatic cells and SSCs.
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Joydeep
J
Das
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Min-Hee
MH
Kang
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Eunsu
E
Kim
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Deug-Nam
DN
Kwon
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Yun-Jung
YJ
Choi
Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology/Animal Resources Research Center, Konkuk University, Seoul 143-701, South Korea.
Jin-Hoi
JH
Kim
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002857:Chromium / Q000494:pharmacology* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D019108:Tight Junctions; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002857:Chromium; C074702:chromium hexavalent ion; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases