Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Toxicol Lett. 2021 May 15;342:38-49. doi: 10.1016/j.toxlet.2021.02.004. Epub 2021 Feb 11.
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.
4-溴二苯醚（BDE3）是多溴二苯醚阻燃剂的光降解产物，被认为是一种内分泌干扰物。然而，目前尚不清楚 BDE3 是否以及如何影响胎儿睾丸的发育。本研究旨在探讨宫内暴露于 BDE3 对大鼠胎儿睾丸发育的影响。从妊娠第 12-21 天开始，BDE3（0、50、100 和 200mg/kg）每天灌胃给怀孕的 Sprague Dawley 大鼠。BDE3 从 50mg/kg 开始显著降低雄性幼鼠的血清睾丸酮水平。BDE3 在 200mg/kg 时减少胎儿睾丸间质细胞数量，而不影响胎儿睾丸间质细胞簇频率和支持细胞数量。此外，BDE3 下调了胎儿睾丸间质细胞基因（Cyp11a1、Hsd3b1、Cyp17a1 和 Hsd17b3）及其蛋白在 100 和/或 200mg/kg 时的表达。RNA-seq 分析显示，对 cAMP 有反应的基因（Ass1、Gpd1、Rpl13a）下调，缺氧相关基因（Egln3 和 P4ha1）上调在 200mg/kg 时。宫内暴露于 BDE3 可通过增加 Beclin1、LC3-II、BAX 的水平，降低 p62 和 BCL2 的水平，促进胎儿睾丸间质细胞的自噬和凋亡。总之，宫内暴露于 BDE3 可阻断胎儿大鼠睾丸的发育。
