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.