Gestational exposure to micro- and nanoplastics leads to poor pregnancy outcomes by impairing placental trophoblast syncytialization

The omnipresent micro- and nanoplastics (MNPs), emerging environmental contaminants, have caused a widespread concern because of their potential threats to public health. Increasing evidence has indicated that MNPs were deeply involved in poor pregnancy outcomes, but the detailed mechanism remains obscure. In this research, we firstly identified that maternal exposure to MNPs during gestation increased both the number and rate of embryo resorption, while reducing embryonic weight, placental diameter and placental weight. This was accompanied by disrupted progesterone and estradiol synthesis in MNPs-treated mouse placentas. In addition, our data suggested that MNPs exposure disturbed placental development, as evidenced by the reduction of the total area of placenta, area of spongiotrophoblast layer and area of labyrinth layer. Subsequently, in vivo and in vitro experiments further indicated that MNPs compromised syncytialization process and decreased the expression of syncytialization markers in mouse placentas and human placental trophoblasts. Further investigation indicated that PERK/eIF2α/ATF4 signaling was activated in MNPs-treated mouse placentas and human placental trophoblasts. More importantly, inhibition of PERK partially restored syncytialization insufficiency caused by MNPs administration. On the whole, our results suggested that gestational exposure to MNPs disturbed placental trophoblasts syncytialization possibly through activating PERK/eIF2α/ATF4 pathway, resulting in aberrant placentation and poor pregnancy outcomes.