Cadmium exposure impaired the uterine decidualization through inducing the imbalance of mitochondrial fusion and fission.

Cadmium (Cd), a widespread environmental pollutant, has toxic effects on spermatogenesis and sperm motility, but its role in uterine decidualization remains unknown. This study revealed that Cd exposure during early pregnancy might impair the uterine decidualization along with the disordered proliferation and apoptosis of stromal cells, resulting in the reduction of mouse neonatal number and birth weight. After disrupting the binding of Ca2+ and LNR-C, Cd exposure ligand-independently activated the NOTCH1 signaling and then restrained the expression of nuclear TAZ via RBPJ-targeting LATS. Further analysis suggested that Cd exposure contributed to the depletion of glutathione via Gclc that was identified as a direct downstream target of TAZ/TEAD, resulting in intracellular ROS accumulation and subsequent mitochondrial dysfunction. Meanwhile, Cd exposure prevented mitochondrial fusion and facilitated mitochondrial fission together with the fragmented mitochondria, whereas attenuation of intracellular ROS alleviated the imbalance between mitochondrial fusion and fission by Cd exposure. Moreover, improvement of mitochondrial fusion insufficiency and excessive fission rescued the impairment of Cd on decidualization. Collectively, Cd exposure impaired the uterine decidualization through inducing the imbalance of mitochondrial fusion and fission. These findings reveal the toxic effect of Cd on female reproduction and serve as a risk factor for adverse pregnancy outcomes.