Polystyrene nanoplastics impair endometrial decidualization via cell cycle arrest and JNK-MAPK pathway-mediated oxidative stress in early pregnant mice.

The ubiquitous polystyrene nanoplastics (PS-NPs) in the environment have emerged as a significant public health concern. Their biological safety, particularly their impact on female fertility, has garnered increasing attention. Our previous study demonstrated that PS-NPs impaired endometrial decidualization. However, the underlying mechanism remains unclear. In this study, we explored the underlying mechanism by which PS-NPs compromised decidualization in early pregnant mice. Our results showed that PS-NPs disrupted uterine decidualization. Specifically, PS-NPs inhibited endometrial cell proliferation and hindered the formation of decidual polyploid cells. Additionally, PS-NPs induced oxidative damage in uteri by disrupting the balance between oxidative stress and antioxidative defenses in the decidua. PS-NPs interfered with the formation of CyclinD1-Cdk4, CyclinE1-Cdk2, CyclinA1-Cdk2, and CyclinB1-Cdk1 complexes, ultimately impairing cell cycle progression at the G1-S and G2-M phases. Inhibition of the JNK-MAPK pathway alleviated excessive oxidative stress in uteri, restored defective decidualization, and improved embryo implantation in PS-NPs-exposed pregnant mice. Further analysis revealed that the JNK-MAPK pathway mediated the PS-NPs-induced suppression of endometrial proliferation. These findings suggested that impaired endometrial proliferation driven by reduced activity of CyclinD1-Cdk4, CyclinE1-Cdk2, CyclinA1-Cdk2, and CyclinB1-Cdk1 complexes may be an important contributor to PS-NPs-induced decidualization defect. Moreover, the JNK-MAPK pathways may be mediators of these detrimental effects.