SF-1 Downregulation and Steroidogenic Disruption in Male Rats Exposed to Silica Nanoparticles (SiO₂) for 90 Days

Silica nanoparticles (SiO₂ NPs) are widely used in biomedical and industrial applications, raising concerns about chronic exposure effects. This study investigated the impact of 90-day oral SiO₂ NP exposure on male reproductive function in Wistar rats (n = 6). In accordance with OECD 408 guidelines and our 14-day range-finding study, doses of 500, 1000, and 2000 mg/kg were selected, with 2000 mg/kg identified as the highest nontoxic level for sub-chronic exposure, and reproductive endpoints including hormone levels, sperm quality, and testicular histopathology were subsequently evaluated. Exposure resulted in significant dose-dependent reductions in body weight, food intake, reproductive organ weights, and serum hormone levels such as testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) (p < 0.001), accompanied by histopathological damage to testicular tissue. Sperm count, vitality, motility, and morphology were significantly and dose-dependently impaired. Enzymatic activities of testicular biomarkers-including acid phosphatase (ACP), glucose-6-phosphate dehydrogenase (G6PD), γ-glutamyl transferase (γ-GT), and succinate dehydrogenase (SDH) were significantly decreased (< 0.001), suggesting metabolic dysfunction. Real-time PCR analyses revealed downregulation of SF-1 and associated steroidogenic genes (HSD3B1, HSD17B10, StAR), which was associated with altered testosterone biosynthesis. The observed SF-1 downregulation was associated with altered steroidogenic regulation, possibly mediated through oxidative and endocrine stress pathways. This study highlights the importance of assessing the long-term safety of SiO₂NPs and their impact on reproductive health, particularly in the context of SF-1-mediated mechanisms.