期刊
TOXICOLOGY AND INDUSTRIAL HEALTH
卷 38, 期 3, 页码 182-191出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/07482337221081206
关键词
BDE47; estrogen receptor; mitochondria; Nrf1; spermatogenesis
资金
- Natural Science Foundation of Jiangsu Province [BK20181273]
This study investigates the mechanism of BDE47 on spermatogenesis in mice. The results indicate that BDE47 impairs testis weight and spermatogenesis, and interferes with the function of mitochondria and germ cells.
2,2 ',4,4 ' -tetrabromodiphenyl ether (BDE47), a well-known endocrine disruptor of the estrogen receptor (ER) is toxic to the mitochondria and spermatogenesis. This study aimed to explore the mechanism of BDE47 on spermatogenesis in mammals. Adult male Institute of Cancer Research (ICR) mice were gavaged daily with BDE47 (0, 1, or 10 mg/kg bw) for 8 weeks. Testicular weight, sperm production and motility, morphology of spermatogenic cells, nuclear respiratory factor 1 (Nrf1) level, and its expression in testes were determined. In vitro, cell viability, and key molecules in the ER-Nrf1-mitochondrial transcription factor A (Tfam)-mitochondria pathway in the immortalized mouse spermatogonia line (GC1) were determined at 48 h and 0-5 h after exposure; RNA interference (RNAi) was also performed to verify that the decreased Nrf1 was associated with mitochondrial dysfunction and the impaired viability of germ cells. The results indicated that BDE47 impaired testis weight and spermatogenesis, impaired mitochondria and germ cells, and decreased Nrf1 in the testes of mice. In vitro, after 48 h exposure, BDE47 reduced cell viability, Nrf1 protein, and mRNA of Nrf1, Tfam, ATP synthase subunit beta (Atp5b), and cytochrome c oxidase subunit I (mt-CO1) in GC1 while also reducing mRNA of Nrf1 and Tfam promptly (from 1 to 5 h) after exposure. Furthermore, Nrf1 RNA interference decreased viability and mitochondrial function in GC1. These results indicated that BDE47 disrupts spermatogenesis in mice, probably by interfering with the ER-Nrf1-Tfam-mitochondria pathway, and Nrf1 is a target molecule of BDE47 estrogen receptor.
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