Pesticide beta-cypermethrin impairs endometrial decidualization and embryo implantation by suppressing autophagy through oxidative stress.

Beta-cypermethrin (β-CYP), a widely used synthetic pyrethroid and potential endocrine disruptor, is linked to adverse reproductive outcomes, yet the mechanisms by which it impairs early pregnancy remain unclear. Endometrial decidualization is often defective in pregnancy loss; however, how β-CYP disrupts this critical process is not fully defined. Here, we investigated the molecular basis of β-CYP-induced implantation failure in mice, focusing on the interplay between oxidative stress (OS) and autophagy in decidualization. Our results demonstrate that β-CYP significantly reduced implantation sites and suppressed decidualization markers both in vivo and in vitro. β-CYP triggered excessive OS in uterine decidua and endometrial stromal cells, as evidenced by elevated reactive oxygen species, malondialdehyde, and lactate dehydrogenase, alongside disruption of the glutathione antioxidant system. Concomitantly, autophagy was inhibited, indicated by a decreased LC3-II/LC3-I ratio, reduced Beclin1, ULK1, and ATG5 levels, and increased P62 accumulation. Mechanistically, OS acted upstream of autophagy suppression; quenching OS with N-Acetylcysteine (NAC) restored autophagic activity and partially rescued decidualization. Conversely, enhancing autophagy with trehalose (Tre), was sufficient to reverse β-CYP-impaired decidualization. The protective effect of NAC was abolished by co-treatment with the autophagy inhibitor 3-Methyladenine (3-MA), confirming that autophagy restoration is required for its rescue effect. Collectively, these findings identify a causal pathway wherein β-CYP-induced OS inhibits autophagy, thereby disrupting endometrial decidualization and compromising embryo implantation.