Oral exposure to polystyrene nanoplastics reduced male fertility and even caused male infertility by inducing testicular and sperm toxicities in mice

Nanoplastics (NPs) are the novel hazardous materials and ubiquitous in environment with different sizes. Although recent studies showed testicular toxicity of PS-NPs, whether and how NPs affect male fertility and whether they have the size-dependent effect remain ambiguous in mammals. In this study, the male mice were orally exposed to 25-, 50-, and 100-nm polystyrene NPs (PS-NPs) for 56 days. All three sized PS-NPs reduced male fertility and even caused male infertility. They accumulated in the testes, induced oxidative stress, affected the expression of apoptosis- and inflammation-related genes, and compromised energy metabolism, resulting in damaged testicular microstructure and functions. PS-NPs caused more severe testicular toxicity in infertile mice than in fertile mice. In addition, PS-NPs inhibited sperm capacitation and capacitation-dependent processes in infertile mice but not in fertile mice. In infertile mice, PS-NPs reduced the sperm levels of two Rho GTPases (RAC1 and CDC42) via increasing their ubiquitination levels and diminished sperm filamentous actin polymerization, thus inhibiting sperm capacitation. However, these testicular and sperm toxicities showed no size-dependent effect among three sized PS-NPs. In conclusion, PS-NPs inhibit male fertility by their multifaceted toxicity on testes and sperm in mice, providing novel insights into reproductive risks of NPs to mammals.