Polystyrene nanoparticles impair endometrial decidualization in early pregnant mice via oxidative stress-driven autophagy suppression and ferroptosis induction.

Polystyrene nanoplastics (PS-NPs) are emerging as potential threats to female reproductive health; however, their impacts on early pregnancy remain poorly understood. This study investigated the effects and underlying mechanisms of PS-NPs exposure on endometrial decidualization in early pregnant mice using both in vivo and in vitro models. Our findings reveal that PS-NPs significantly reduced the number of embryo implantation sites and impaired decidualization. PS-NPs caused defective autophagy characterized by enhanced initiation but impaired completion, and simultaneously trigger ferroptosis via glutathione peroxidase 4 inactivation and iron overload. Notably, pharmacological rescue experiments demonstrate that reactive oxygen species act as the upstream trigger, while autophagy dysfunction and ferroptosis collectively contribute to decidualization defects, with ferroptosis serving as a terminal effector pathway. Strikingly, single or double interventions with the ROS scavenger N-acetylcysteine, the autophagy agonist trehalose, or the ferroptosis inhibitor ferrostatin 1 only partially restored the decidualization marker. In contrast, the simultaneous application of three interventions-ROS inhibition, autophagy activation, and ferroptosis inhibition-substantially reversed PS-NPs-induced decidualization defects. Our findings revealed that PS-NPs compromised decidualization by suppressing autophagy and inducing ferroptosis through oxidative stress. These findings provide novel insights into the reproductive toxicity of nanoplastics, identifying them as a significant risk factor for early pregnancy maintenance.