Exposure to titanium dioxide nanoparticles disrupts the BTB by interfering with the assembly of stress granules in germ cells.

Titanium dioxide nanoparticles (TiO NPs) are among the most prevalent nanomaterials utilized in industrial and medical fields. However, their impact on spermatogenesis and male fertility remains insufficiently characterized. This study addresses the reproductive toxicity of TiO NPs and elucidates the underlying molecular mechanisms involved. Our findings demonstrate that exposure to TiO NPs leads to a significant reduction in sperm count and motility. Specifically, TiO NPs disrupt the integrity of the blood-testis barrier (BTB) and compromise the cytoskeletal structure in both spermatogenic and Sertoli cells. Additionally, treatment with TiO NPs is associated with cell death and a decrease in the protein levels of BTB-related components, including N-cadherin, β-catenin, occludin, and ZO-1. Mechanistic investigations reveal that TiO NPs inhibit stress granule formation in germ cells subjected to heat stress and promote germ cell apoptosis via activation of the ATM/P53 signaling pathway. Collectively, our study highlights a potential connection between environmental health and reproductive health, revealing multiple detrimental effects of TiO NPs and uncovering previously unrecognized mechanisms by which nanomaterials may adversely impact the reproductive system.