Abstract

This study attempts to explore the potential impact of titanium dioxide nanoparticles (n-TiO₂) on bioconcentration and reproductive impairments of male zebrafish in the presence of 2,2′,4,4′-tetrabromodiphenyl ether (BDE47), the congener of PBDEs predominant in environment and most abundant in biosamples. n-TiO₂ nanoparticles strongly adsorbed BDE47 to form BDE47/TiO₂ complex, which was taken up into the testes of zebrafish, and increased the tissue burdens of both BDE47 and n-TiO₂. Correspondingly, no observed toxic dose of n-TiO₂ (100 μg/L) was found to aggravate the abnormal histological morphology of the testes and the decrease in egg production, gonadosomatic index, sexual hormone levels and related gene expression in zebrafish in the presence of BDE47 at 5 or 50 μg/L. In addition, n-TiO₂ exacerbated the destruction resulting from the ultrastructural disassembly of intercellular connectivity of germ cells in zebrafish and the decrease in transepithelial electrical resistance in TM4 cells induced by BDE47. Furthermore, n-TiO₂ enhanced BDE47 to initially activate p-JNK MAPK signaling pathway and subsequently triggered the downregulation of junction proteins (i.e., ZO-1, Connexin-43 and N-cadherin), leading to impaired cell-cell junctions in vivo and in vitro. Our results demonstrated that n-TiO₂ should act as a carrier to facilitate the accumulation of BDE47 in zebrafish testes and result in a synergistic effect on BDE47-induced adverse reproductive outcomes via disruption of intercellular connectivity of zebrafish testes. This study is beneficial in providing a scientific basis for improving the health risk assessment of environmental pollutants, particularly those that coexist with nanoparticle contamination in realistic environments.

摘要

本研究试图探讨二氧化钛纳米粒子 (n-TiO ₂ ) 在多溴二苯醚的同系物 2,2',4,4'-四溴二苯醚 (BDE47) 存在下对雄性斑马鱼的生物浓度和生殖障碍的潜在影响在环境中占主导地位，在生物样品中含量最高。n-TiO ₂纳米颗粒强烈吸附BDE47 形成BDE47/TiO ₂复合物，该复合物被吸收到斑马鱼的睾丸中，并增加了BDE47 和n-TiO ₂的组织负荷。相应地，未观察到 n-TiO _{2 的}毒性剂量(100 μg/L) 被发现在 5 或 50 μg/L 的 BDE47 存在下会加剧斑马鱼睾丸的异常组织学形态和产蛋量、性腺指数、性激素水平和相关基因表达的下降。此外，n-TiO ₂加剧了斑马鱼生殖细胞细胞间连接的超微结构解体和BDE47诱导的TM4细胞跨上皮电阻降低导致的破坏。此外，n-TiO ₂增强 BDE47 以最初激活 p-JNK MAPK 信号通路，随后触发连接蛋白（即 ZO-1、Connexin-43 和 N-钙粘蛋白）的下调，导致体内细胞-细胞连接受损和体外. 我们的研究结果表明，n-TiO ₂应该作为一种载体，促进 BDE47 在斑马鱼睾丸中的积累，并通过破坏斑马鱼睾丸的细胞间连接对 BDE47 诱导的不良生殖结果产生协同作用。该研究有利于为改善环境污染物的健康风险评估提供科学依据，特别是在现实环境中与纳米颗粒污染共存的污染物。