Exposure to glyphosate-based herbicide impairs uterine decidualization via disruption of autophagy-adhesion molecules-uNK cell residence in mice

Glyphosate-based herbicides (GBH) are the most widely used herbicides worldwide. Epidemiological studies have suggested that maternal exposure to GBH is associated with reduced fertility and shortened gestational length. However, the impact of GBH on uterine decidualization, a process essential for embryo implantation and pregnancy maintenance, remains poorly characterized. Therefore, this study aimed to investigate the effects and mechanisms of action of GBH on uterine decidualization. Mice were orally exposed to 0, 5, or 50 mg·kg-1·day-1 GBH from normal pregnancy and pseudopregnancy days 0.5-7.5. The results showed that GBH exposure significantly reduced embryo implantation and uterine weight, concurrently impairing the decidualization process. Further studies indicated that GBH suppressed uterine autophagy, downregulated adhesion-related genes, diminished uterine natural killer (uNK) cell residence, and compromised decidual angiogenesis. Notably, the autophagy inducer rapamycin ameliorated the reduction in embryo implantation and uterine weight, accompanied by the upregulation of autophagy proteins, adhesion-related genes, and uNK cell residence in the uteri. In conclusion, our data suggest that maternal exposure to GBH impairs uterine decidualization via the disruption of autophagy-adhesion molecules-uNK cell residence in mice.