2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), a representative congener of polybrominated diphenyl ethers in the environment, is known to have reproductive toxicity. However, the underlying mechanisms remain to be clarified, especially in in vivo systems. In the present study, we employed Caenorhabditis elegans to study the effects of BDE-47 on reproduction. Our results showed that BDE-47 impaired worm fecundity and induced germ cell apoptosis. To elucidate the mechanisms, DNA damage and oxidative stress induction were investigated by determining the numbers of foci formation in transgenic worms expressing HUS-1::GFP and the levels of reactive oxygen species, respectively. We found that BDE-47 induced oxidative stress but not DNA damage, and treatment with the antioxidant, N-acetyl-L-cysteine, completely abrogated BDE-47-induced germ cell apoptosis. In addition, the apoptosis was blocked in mutants carrying mek-1, sek-1 or abl-1 loss-of-function alleles, but not in the p53/cep-1 deficient worms, suggesting that the mitogen-activated protein kinase (MAPK) signaling cascade was essential for BDE-47-induced germ cell apoptosis and p53/cep-1 was not required. Moreover, the apoptosis in the strains deficient for DNA damage response was not suppressed under BDE-47 treatment. Overall, we demonstrated that BDE-47 could induce oxidative stress and subsequent germ cell apoptosis in Caenorhabditis elegans through a MAPK-mediated p53-independent pathway.

2,2'，4,4'-四溴二苯醚（BDE-47）是环境中多溴二苯醚的代表性同源物，已知具有生殖毒性。但是，其潜在机制仍有待阐明，尤其是在体内系统中。在本研究中，我们采用秀丽隐杆线虫研究了BDE-47对生殖的影响。我们的结果表明，BDE-47损害蠕虫的繁殖力并诱导生殖细胞凋亡。为了阐明机理，通过确定分别表达HUS-1 :: GFP的转基因蠕虫的病灶形成数量和活性氧水平，研究了DNA损伤和氧化应激诱导。我们发现BDE-47会诱导氧化应激，但不会引起DNA损伤，并使用抗氧化剂进行处理，N-乙酰基-L-半胱氨酸完全消除了BDE-47诱导的生殖细胞凋亡。此外，在携带mek-1，sek-1或abl-1功能丧失等位基因的突变体中，凋亡被阻断，但在p53 / cep-1缺陷蠕虫中却未被阻断，这表明有丝分裂原激活的蛋白激酶（MAPK ）信号级联对于BDE-47诱导的生殖细胞凋亡至关重要，并且不需要p53 / cep-1。而且，在BDE-47处理下，不能抑制DNA损伤应答的菌株中的细胞凋亡被抑制。总体而言，我们证明了BDE-47可以诱导秀丽隐杆线虫的氧化应激和随后的生殖细胞凋亡 通过MAPK介导的不依赖p53的途径。