Nano-Titanium Dioxide Induces Ovarian Function Damage in Mice by Mediating Granulosa Cell Apoptosis

The accumulation of nanoparticles (NPs) in the female body has raised global concerns regarding potential effects on the reproductive system. This study aimed to investigate the toxic effects of nano-titanium dioxide (nano-TiO₂) exposure on the ovaries and the underlying mechanisms. By establishing a nano-TiO₂ accumulation model in mice, our research systematically evaluated the effects of different concentrations of nano-TiO₂ exposure on the development and reproductive endocrine functions of mice. The results showed that nano-TiO₂ exposure significantly reduced the littering rate, sex hormone levels, and ovarian index of mice, and the effects were dose-dependent. Studies on the mechanisms involved revealed that nano-TiO₂ induces an excessive production of reactive oxygen species (ROS), leading to the potential collapse of the mitochondrial membrane and an increase in the apoptosis rate of granulosa cells, thereby triggering oxidative stress and inhibiting the expression of ovarian-specific genes and granulosa-cell function genes. This study reveals the "dual blow" mechanism of nano-TiO₂-mediated ovarian morphology and function through oxidative stress in granulosa cells, namely directly disrupting cellular homeostasis and interfering with the reproductive-related gene network, ultimately leading to decreased ovarian function. This provides experimental evidence for assessing the reproductive risks of nanomaterials in women.