Inhibition of testosterone synthesis induced by oral TiO₂ NPs is associated with ROS-MAPK(ERK1/2)-StAR signaling...

Titanium dioxide nanoparticles (TiO₂ NPs) have been widely used in food, medical, and other fields; their reproductive toxicity has been reported in numerous studies. However, the relevant toxicity mechanism still requires further exploration. In this paper, the effect of oral exposure to 500 mg/kg TiO₂ NPs (anatase and rutile) in adult male SD rats was studied over 3 and 7 days. Results showed that the total sperm count and testosterone level of 7 days of exposure in serum decreased in the experimental group. Testicular tissue lesions, such as disappearance of Leydig cells, disorder of arrangement of spermatogenic cells in the lumen of convoluted seminiferous tubules, and disorder of arrangement of germ cells, were observed. Meanwhile, the expression of steroidogenic acute regulatory (StAR; the key factors of testosterone synthesis), MAPK (ERK1/2), and phosphorylated ERK1/2 in testes of SD rats after exposure to TiO₂ NPs for 7 days decreased, while the malondialdehyde content increased and superoxide dismutase activity decreased in serum. The present study showed that TiO₂ NPs could cause reproductive toxicity. Notably, anatase is more toxic than rutile. In addition, exposure to 500 mg/kg TiO₂ NPs for 7 days inhibited testosterone synthesis in male rat, which may be related to the reactive oxygen species (ROS)-MAPK (ERK1/2)-StAR signal pathway. Warning that the use of TiO₂ NPs should be regulated.