Large diameter zinc oxide nanoparticles reduced testicular CYP17A1 and viability and elevated testicular inflammation in adult male rats

Abstract Background The rapid advancement of nanotechnology has led to growing interest in its effects on health. This study investigates the impact of zinc oxide nanoparticles (ZnO NPs) on male rats’ reproductive health by assessing two different sizes (40 nm and 70 nm) in comparison to bulk ZnO and untreated controls. Methods Adult male rats ( n = 8 per group) were randomly assigned to four groups: a control group, a group receiving bulk ZnO (150 mg/kg), and two groups receiving ZnO NPs of 40 nm and 70 nm, respectively, also at 150 mg/kg. Results Treatments were administered via oral gavage for 50 days. ZnO and ZnO NPs caused reductions in body weight, sperm count, motility, and serum levels of luteinizing hormone (LH) and testosterone. Testicular levels of CYP17A1 and CYP1B1, along with p53 and cdk1 expression, decreased, while caspase 3 activity and serum acid phosphatase and ALT levels increased. ZnO NPs (both sizes) raised relative testis weight, myeloperoxidase, and lowered serum follicle stimulating hormone and testicular malondialdehyde. No effects were observed on testicular zinc, GSH, or SOD. ZnO NPs lowered LH, disrupting testosterone production by reducing CYP17A1 and CYP1B1 activity. The nanoparticles also increased testicular inflammation, lowered cell viability, and negatively impacted sperm motility and morphology. Conclusion Zinc oxide nanoparticles, particularly larger-sized ones, impaired male reproductive health by reducing LH levels and downregulating CYP17A1 and CYP1B1, key enzymes in androgen and estrogen metabolism. These hormonal disruptions, driven by inflammation rather than oxidative stress, led to decreased testosterone synthesis, poor sperm quality, and increased abnormalities.