Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells.
Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have a deleterious effect on the male reproductive system in animals besides delayed neurotoxicity. Our preliminary results found that TOCP could disrupt the seminiferous epithelium in the testis and inhibit spermatogenesis, but the precise mechanism is yet to be elucidated. This study shows that TOCP inhibited viability of rat spermatogonial stem cells in a dose-dependent manner. TOCP could not lead to cell cycle arrest in the cells; the mRNA levels of p21, p27, p53, and cyclin D1 in the cells were also not affected by TOCP. Meanwhile, TOCP did not induce apoptosis of rat spermatogonial stem cells. After treatment with TOCP, however, both LC3-II and the ratio of LC3-II/LC3-I were markedly increased; autophagy proteins ATG5 and beclin 1 were also increased after treatment with TOCP, indicating that TOCP could induce autophagy in the cells. Ultrastructural observation under the transmission electron microscopy indicated that autophagic vesicles in the cytoplasm containing extensively degraded organelles such as mitochondria and endoplasmic reticulum increased significantly after the cells were treated with TOCP. In summary, we have shown that TOCP can inhibit viability of rat spermatogonial stem cells and induce autophagy of the cells, without affecting cell cycle and apoptosis.
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Meng-Ling
ML
Liu
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Jing-Lei
JL
Wang
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Jie
J
Wei
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Lin-Lin
LL
Xu
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Mei
M
Yu
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Xiao-Mei
XM
Liu
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China.
Wen-Li
WL
Ruan
Department of PhysiologyMedical College of Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, People's Republic of ChinaMedical Research CenterThe First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of ChinaLibraryMedical College of Nanchang University, Nanchang 330006, People's Republic of ChinaNursing School of Jiujiang UniversityJiujiang 332000, People's Republic of China chenjiaxiang@ncu.edu.cn.
Jia-Xiang
JX
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D046529:Microscopy, Electron, Transmission; D011506:Proteins / Q000032:analysis; D051381:Rats; D013093:Spermatogonia / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D013234:Stem Cells / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D014317:Tritolyl Phosphates / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; C545865:Atg5 protein, rat; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; C512829:Becn1 protein, rat; D011506:Proteins; D014317:Tritolyl Phosphates; C025541:tri-o-cresyl phosphate