Bioaccumulation of BDE47 in testes by TiO2 nanoparticles aggravates the reproductive impairment of male zebrafish by disrupting intercellular junctions

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.