Gestational Exposure to Ultrafine Particles Reveals Sex- and Dose-Specific Changes in Offspring Birth Outcomes, Placental Morphology, and Gene Networks

Abstract

Abstract Particulate matter (PM) causes adverse developmental outcomes following prenatal exposure, but the underlying biological mechanisms remain uncertain. Here we elucidate the effects of diesel exhaust ultrafine particle (UFP) exposure during pregnancy on placental and fetal development. Time-mated C57Bl/6n mice were gestationally exposed to UFPs at a low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) for 6 h daily. Phenotypic effects on fetuses and placental morphology at gestational day (GD) of 18.5 were evaluated, and RNA sequencing was characterized for transcriptomic changes in placental tissue from male and female offspring. A significant decrease in average placental weights and crown to rump lengths was observed in female offspring in the LD exposure group. Gestational UFP exposure altered placental morphology in a dose- and sex-specific manner. Average female decidua areas were significantly greater in the LD and HD groups. Maternal lacunae mean areas were increased in the female LD group, whereas fetal blood vessel mean areas were significantly greater in the male LD and HD groups. RNA sequencing indicated several disturbed cellular functions related to lipid metabolism, which were most pronounced in the LD group and especially in female placental tissue. Our findings demonstrate the vulnerability of offspring exposed to UFPs during pregnancy, highlighting sex-specific effects and emphasizing the importance of mitigating PM exposure to prevent adverse health outcomes.