Ambient fine particulate matter exposure disrupts placental autophagy and fetal development in gestational mice

Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM2.5). However, potential mechanism remains to be elucidated. In the present study, pregnant C57BL/6 mice were randomly assigned to be exposed to either filtered air or ambient PM2.5 in the gestation period via a concentrated whole-body exposure system. We found that gestational PM2.5 exposure exerted no effect on implantation, preterm delivery, as well as fetal resorption and death. However, in utero fetal exposure to PM2.5 showed a significant reduction in body weight and crown-rump length on GD13 and GD18. Meanwhile, maternal blood sinusoid in placenta was markedly reduced along with abnormal expression of placental nutrient transporters and growth hormone in dams exposed to PM2.5. Additional tests showed gestational PM2.5 exposure decreased autophagy-related protein levels and inhibited autophagy flux mainly on GD15. Correspondingly, AMPK/mTOR signaling pathway, a critical negative regulator of autophagy, was activated in placenta on GD15 by PM2.5 exposure as well. These findings provide evidences that placental developmental disorder caused by autophagy inhibition might be an important mechanism for the growth restriction caused by PM2.5 exposure.