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

Titanium dioxide nanoparticles (TiO₂ 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 TiO₂ NPs and elucidates the underlying molecular mechanisms involved. Our findings demonstrate that exposure to TiO₂ NPs leads to a significant reduction in sperm count and motility. Specifically, TiO₂ NPs disrupt the integrity of the blood-testis barrier (BTB) and compromise the cytoskeletal structure in both spermatogenic and Sertoli cells. Additionally, treatment with TiO₂ 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 TiO₂ 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 TiO₂ NPs and uncovering previously unrecognized mechanisms by which nanomaterials may adversely impact the reproductive system.