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 PM(2.5 )exposure.

Automated summary

Recent studies have found that gestational exposure to ambient fine particulate matter (PM2.5) is associated with adverse pregnancy outcomes, particularly intrauterine growth restriction (IUGR). However, the underlying mechanism is still unclear. In this study, pregnant mice were exposed to either filtered air or ambient PM2.5, and it was found that PM2.5 exposure during gestation resulted in reduced fetal body weight and crown-rump length. Moreover, the placental blood sinusoid and expression of placental nutrient transporters and growth hormone were also affected by PM2.5 exposure. Additional tests revealed that PM2.5 exposure inhibited autophagy and activated the AMPK/mTOR signaling pathway in the placenta. These findings suggest that autophagy inhibition leading to placental developmental disorder might be an important mechanism for PM2.5-induced growth restriction.