Sex-Dependent Bioaccumulation of Nano Zinc Oxide and Its Adverse Effects on Sexual Behavior and Reproduction in Japanese Medaka

This study investigated the adverse effects of 200 nm zinc oxide particles (nZnO) on sexual behavior and reproduction in Japanese medaka in comparison with ZnSO4 and correlated the consequences with the bioaccumulation pattern of the particles in associated organs. nZnO exposure impaired sexual and territorial behaviors and affected fertility by altering sperm viability and motility in males through reactive oxygen species (ROS) induction. Conversely, none of these effects other than behavior loss was seen in males exposed to ZnSO4. nZnO exposure to females induced ROS in ovaries, causing follicular growth arrest, atresia, and subfertility. Further, sexsteroid levels were altered by both nZnO and ZnSO4 in males and by nZnO but not ZnSO4 in females. Biodistribution studies revealed the deposition of nZnO as particulate matter in the brain, gills, gut, kidney, and ovary. Particle accumulation in the brain was sex specific, as the particles were found in the brain of males but not that of females. A similar trend was seen for zinc levels in males and females exposed to ZnSO4. Importantly, the female sex hormone, 17 beta-estradiol was found to prevent nZnO accumulation in the female brain, emphasizing the need for biodistribution profiling of nanoparticle-based drug delivery vehicles separately in males and females before they are commercialized. This study has demonstrated that the toxic effects of nZnO on the reproductive system were mainly caused by ROS induction, while zinc ions were predominantly responsible for the adverse impact of ZnSO4.