title: Endosulfan inhibiting the meiosis process via depressing expressions of regulatory factors and causing cell cycle arrest in spermatogenic cells.
abstract: Endosulfan is a persistent organic pollutant and widely used in agriculture as a pesticide. It is present in air, water, and soil worldwide; therefore, it is a health risk affecting especially the reproductive system. The aim of this study was to evaluate the toxicity of endosulfan in the reproductive system. To investigate the effect of endosulfan on meiosis process, 32 rats were divided into four groups, treated with 0, 1, 5, and 10 mg/kg/day endosulfan, respectively, and sacrificed after the 21 days of treatments. Results show that endosulfan caused the reductions in sperm concentration and motility rate, which resulted into an increased in sperm abnormality rate; further, endosulfan induced downregulation of spermatogenesis- and oogenesis-specific basic helix-loop-helix transcription factor (Sohlh1) which controls the switch on meiosis in mammals, as well cyclin A1, cyclin-dependent kinases 1 (CDK1), and cyclin-dependent kinases 2 (CDK2). In vitro, endosulfan induced G2/M phase arrest in the spermatogenic cell cycle and caused proliferation inhibition. Moreover, endosulfan induced oxidative stress and DNA damage in vivo and vitro. The results suggested that endosulfan could inhibit the start of meiosis by downregulating the expression of Sohlh1 and induce G2/M phase arrest of cell cycle by decreasing the expression of cyclin A1, CDK1, and CDK2 via oxidative damage, which inhibits the meiosis process, and therefore decrease the amount of sperm.
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Fang-Zi
authors.initials: FZ
authors.lastname: Guo
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Lian-Shuang
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Jia-Liu
authors.initials: JL
authors.lastname: Wei
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ren
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China. jingli12@163.com.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. jingli12@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmen Wai, Fengtai District, Beijing, 100069, People's Republic of China. xqzhou@ccmu.edu.cn.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. xqzhou@ccmu.edu.cn.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004726:Endosulfan / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D004726:Endosulfan
keywords: Cell cycle arrest; Endosulfan; Meiosis process; Meiosis start; Rat; Spermatogenic cell