Exposure to 4-bromodiphenyl ether during pregnancy blocks testis development in male rat fetuses. (15th May 2021)

• Record Type: Journal Article
• Authors: Li, Yang; Ma, Feifei; Li, Zengqiang; Yu, Yige; Yan, Haoni; Tahir, Anam; Zheng, Wenwen; Li, Xiaoheng; Huang, Tongliang; Ge, Ren-Shan
• Is Part Of: Toxicology letters. Volume 342(2021)
• Page Start: 38
• Page End: 49
• Publication Date: 2021-05-15
• Subjects: 4-bromodiphenyl ether -- Testosterone -- RNA-seq -- Fetal leydig cell -- Apoptosis -- Autophagy; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.02.004
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: BDE3 inhibits fetal Leydig cell development. BDE3 lowers testosterone production in fetal testis. BDE3 reduces fetal Leydig cell number. BDE3 induces autophagy and apoptosis signaling in fetal testis. Abstract: 4-Bromodiphenyl ether (BDE3) is a photodegradation product of higher polybrominated diphenyl ether flame retardants and is known as an endocrine disruptor. However, it is unclear whether and how BDE3 affects the development of fetal testes. This study aimed to investigate the effect of in utero exposure to BDE3 on fetal testicular development in rats. From gestational day (GD) 12–21, BDE3 (0, 50, 100, and 200 mg/kg) was daily gavaged to female pregnant Sprague Dawley rats. BDE3 significantly reduced serum testosterone levels of male pups starting at 50 mg/kg. BDE3 reduced fetal Leydig cell number at a dose of 200 mg/kg without affecting fetal Leydig cell cluster frequency and Sertoli cell number. In addition, BDE3 down-regulated the expression of fetal Leydig cell genes ( Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 ) and their proteins at 100 and/or 200 mg/kg. RNA-seq analysis showed that genes responsive to cAMP ( Ass1, Gpd1, Rpl13a ) were down-regulated and hypoxia-related genes ( Egln3 and P4ha1 ) were up-regulated at 200 mg/kg. In utero exposure to BDE3 can promote autophagy and apoptosis of fetal Leydig cells via increasing the levels of Beclin1, LC3-II, BAX, and by decreasing the levels of p62 and BCL2. In conclusion, in utero exposure to BDE3 blocks the development of fetal rat testes.