Polystyrene nanoparticles induced adverse pregnancy outcomes via the activation of placental ferroptosis and gut microbiota dysfunction

Maternal exposure to microplastics, particularly polystyrene nanoparticles (PS-NPs), is an emerging environmental threat associated with adverse pregnancy outcomes. However, the underlying mechanisms, especially the potential involvement of placental ferroptosis and gut microbiota, remain largely unexplored. This study aimed to elucidate whether and how maternal exposure to 50-nm PS-NPs disrupts pregnancy in a mouse model, with a focus on gut microbiota dysbiosis and placental ferroptosis. We found that PS-NPs exposure during pre-mating and gestation induced gut microbiota dysbiosis (e.g., increased Campylobacterota and Helicobacter) and triggered placental ferroptosis, as evidenced by iron accumulation, lipid peroxidation, and dysregulation of key proteins associated with ferroptosis. These cellular disruptions led to impaired placental barrier function, increased inflammation, and ultimately, adverse pregnancy outcomes, including elevated embryo resorption and reduced fetal weight. Crucially, correlation analysis linked specific gut microbiota alterations to ferroptosis and pregnancy loss. Furthermore, in vitro experiments confirmed that ferroptosis inhibitors alleviated PS-NPs-induced trophoblast dysfunction. These results suggest that maternal exposure to PS‑NPs may contribute to adverse pregnancy outcomes via inducing gut‑microbiota dysbiosis and placental ferroptosis, which might be potential focus for future mechanistic and therapeutic investigations.