Exposure to Titanium Dioxide Nanoparticles Leads to Specific Disorders of Spermatid Elongation via Multiple Metabolic...

Titanium dioxide nanoparticles (TiO₂ NPs) have been extensively utilized in various applications. However, the regulatory mechanism behind the reproductive toxicity induced by TiO₂ NP exposure remains largely elusive. In this study, we employed a Drosophila model to assess potential testicular injuries during spermatogenesis and conducted bulk RNA-Seq analysis to elucidate the underlying mechanisms. Our results reveal that while prolonged exposure to lower concentrations of TiO₂ NPs (0.45 mg/mL) for 30 days did not manifest reproductive toxicity, exposure at concentrations of 0.9 and 1.8 mg/mL significantly impaired spermatid elongation in Drosophila testes. Notably, bulk RNA-seq analysis revealed that TiO₂ NP exposure affected multiple metabolic pathways including carbohydrate metabolism and cytochrome P450. Importantly, the intervention of glutathione (GSH) significantly protected against reproductive toxicity induced by TiO₂ NP exposure, as it restored the number of Orb-positive spermatid clusters in Drosophila testes. Our study provides novel insights into the specific detrimental effects of TiO₂ NP exposure on spermatid elongation through multiple metabolic alterations in Drosophila testes and highlights the protective role of GSH in countering this toxicity.