title: 4-Bromodiphenyl Ether Induces Germ Cell Apoptosis by Induction of ROS and DNA Damage in Caenorhabditis elegans.
abstract: Polybrominated diphenyl ethers may affect male reproductive function; however, the underlying mechanism is still uncertain. By using Caenorhabditis elegans, a commonly used model to study basic biological processes in apoptosis, we investigated the toxic effects of 4-bromodiphenyl ether (BDE-3), the most fundamental mono-BDE generated from degradation of polybrominated diphenyl ethers in the environment. We found that BDE-3 treated worms exhibited decreased life spans, impaired fecundity and delayed egg laying. BDE-3 induced dose-dependent germ cell apoptosis in wild-type N2 strain; however, this effect was blocked in mutants of p53/cep-1 and DNA damage response gene hus-1. Moreover, the knockout of the MAPK kinases (mutants mek-1 and sek-1) and the p53 antagonist protein ABL-1 (abl-1), which are essential for stress-induced germ cell apoptosis, also abrogated the germ cell apoptosis induced by BDE-3. Generation of reactive oxygen species (ROS) in intact animals was determined by a fluorescent probe, 2,7-dichlorofluorescein diacetate, and the ROS level was significantly elevated by BDE-3 treatment. Microarray analysis on gene expression profiles further revealed the possible pathways involved in BDE-3 toxicity. Overall, our findings suggested that BDE-3 could induce reproductive dysfunction and germ cell apoptosis in C. elegans by induction of ROS and DNA damage.
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: You
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xi
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Urology, Tong Ren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D005854:Germ Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects
chemical_list: C000626479:4-bromodiphenyl ether; D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species
keywords: BDE-3; C. elegans; DNA damage; ROS; germ cell apoptosis