Li Yuan-Yuan, Xiong Yi-Ming, Zhang Shu-Yan, Deng Jing-Lin, Xue Qiao, Hou Xing-Wang, Liu Wen-Bin, Li Xing-Hong, Qin Zhan-Fen
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Environ Health (Wash). 2023 Jun 22;1(3):168-179. doi: 10.1021/envhealth.3c00044. eCollection 2023 Sep 15.
Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a widely used flame retardant, has been frequently detected in various environmental compartments, but its health hazard remains largely unknown. Here, we investigated the adverse effects of TBBPA-BDBPE (50 and 1000 μg/kg/day) on postnatal testis development in CD-1 mice and the underlying mechanism. Following the first week of maternal exposure, neonatal mice in the high-dose group exhibited reduced seminiferous tubule area, fewer Sertoli cells and germ cells, and damaged microtubules in Sertoli cells; even microtubule damage was also observed in the low-dose group. When exposure extended to adulthood, male offspring in the high-dose group presented more remarkable alterations in reproductive parameters, including reduced sperm count; in the low-dose group, microtubule damage was also observable, along with blood-testis barrier impairment. Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization. Moreover, we observed attenuated microtubules in mouse Sertoli cells (TM4) following TBBPA-BDBPE treatment, suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics. This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.
四溴双酚A - 双（2,3 - 二溴丙基醚）（TBBPA - BDBPE）是一种广泛使用的阻燃剂，已在各种环境介质中频繁检测到，但其健康危害在很大程度上仍不为人知。在此，我们研究了TBBPA - BDBPE（50和1000μg/kg/天）对CD - 1小鼠出生后睾丸发育的不良影响及其潜在机制。在母体暴露的第一周后，高剂量组的新生小鼠表现出曲细精管面积减小、支持细胞和生殖细胞数量减少以及支持细胞中的微管受损；甚至在低剂量组也观察到了微管损伤。当暴露延长至成年期时，高剂量组的雄性后代在生殖参数方面出现了更显著的变化，包括精子数量减少；在低剂量组中，也可观察到微管损伤以及血睾屏障受损。进一步的分子对接分析和微管蛋白聚合试验表明，TBBPA - BDBPE可与微管蛋白相互作用并破坏其聚合。此外，我们观察到TBBPA - BDBPE处理后的小鼠支持细胞（TM4）中的微管减少，这表明TBBPA - BDBPE可能通过干扰微管蛋白动力学来损害睾丸发育。本研究不仅突出了TBBPA - BDBPE对雄性生殖的危害，还极大地增进了对化学物质雄性生殖毒性分子机制的理解。
