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.