Geng Xiya, Wei Yu, Geng Wenfeng, Zhang Taifa, Ding Tao, Xu Jixiang, He Huan, Gao Xin, Zhai Jinxia
Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Meishan Rd 81, Hefei, 230032, China.
The First Affiliated Hospital of Anhui Medical University, Jixi Rd 218, Hefei, 230032, China.
Environ Sci Pollut Res Int. 2023 Apr;30(16):47349-47365. doi: 10.1007/s11356-023-25476-w. Epub 2023 Feb 4.
Deca brominated diphenyl ether (BDE-209) is a widely used flame retardant with endocrine-disrupting activity which reportedly caused sperm quality decline and damaged blood-testis barrier (BTB). However, whether BDE-209 exposure led to BTB integrity dysfunction through affecting microtubule cytoskeletal organization and junctions was not well-elucidated. This study aimed to investigate the role of estrogen receptor α (ERα) in BDE-209-mediated perturbation of BTB integrity. Male rats and primary culture Sertoli cells were co-treated with BDE-209 and propylpyrazoletriol (PPT). The data demonstrated that BDE-209 impaired BTB integrity by reducing crucial tight junction-related proteins with ZO-1 and Occludin. Furthermore, the data suggested that BDE-209 diminished the apical ectoplasmic specialization markers with Eps8 and Formin1. In addition, BDE-209 damaged BTB ultrastructure including tight junctions and ectoplasmic specialization structures with broken tight junctions and the absence of actin microfilaments. Further experiments revealed that ERα was triggered in BDE-209-treated Sertoli cells. Unexpectedly, we found that PPT rescued BDE-209-mediated disruption of BTB integrity including tight junction and apical ectoplasmic specialization by activating ERα in Sertoli cells. Taken together, these findings indicated that intratesticular BDE-209 exposure perturbed BTB integrity and destroyed BTB structure by blocking ERα pathway. Our findings provide a new therapeutic target for male reproductive dysfunction.
十溴二苯醚（BDE - 209）是一种广泛使用的具有内分泌干扰活性的阻燃剂，据报道它会导致精子质量下降并损害血睾屏障（BTB）。然而，BDE - 209暴露是否通过影响微管细胞骨架组织和连接导致BTB完整性功能障碍尚未得到充分阐明。本研究旨在探讨雌激素受体α（ERα）在BDE - 209介导的BTB完整性扰动中的作用。将雄性大鼠和原代培养的支持细胞用BDE - 209和丙基吡唑三醇（PPT）共同处理。数据表明，BDE - 209通过减少关键的紧密连接相关蛋白如闭锁小带蛋白1（ZO - 1）和闭合蛋白，损害了BTB的完整性。此外，数据表明BDE - 209减少了顶端外质特化标记物如表皮生长因子受体底物8（Eps8）和formin1。另外，BDE - 209破坏了BTB超微结构，包括紧密连接和外质特化结构，出现紧密连接断裂和肌动蛋白微丝缺失的情况。进一步的实验表明，在BDE - 209处理的支持细胞中ERα被激活。出乎意料的是，我们发现PPT通过激活支持细胞中的ERα挽救了BDE - 209介导的BTB完整性破坏，包括紧密连接和顶端外质特化。综上所述，这些发现表明睾丸内BDE - 209暴露通过阻断ERα途径扰乱了BTB完整性并破坏了BTB结构。我们的发现为男性生殖功能障碍提供了一个新的治疗靶点。
