Urban air pollution disrupts placental microarchitecture and shifts hofbauer cells towards a pro-inflammatory state

Abstract

Exposure to urban air pollution during early pregnancy is associated with increased risk for adverse pregnancy outcomes, such as preeclampsia (PE), and there is an urgent need to understand how air pollution affects biological mechanisms in the placenta. Hofbauer cells (HBCs) are fetal placental macrophages that regulate immune tolerance in the placenta. They are normally polarized towards an anti-inflammatory M2 phenotype but display a more pro-inflammatory M1 phenotype in PE. The ex vivo dual placental perfusion approach uses full term human placentas to study physiological aspects of the placenta. In this study, effects of urban traffic-derived particles of size <2.5 µm (PM2.5) on placental tissue and HBC polarization was deciphered. To study changes in placental microarchitecture and cell morphology, transmission electron microscopy was applied. In addition, changes in cell surface markers on HBCs were determined by immunohistochemistry. Exposure to PM2.5 caused disrupted collagen structures and affected cell organelles in multiple cell types inside placental villi. The resident HBC marker CD163 was not affected by PM2.5 exposure, while CD206 was reduced by 60 % and CD209 remained unchanged, indicating altered M2 polarization. Additionally, the expression of pro-inflammatory M1 markers CD40 (p = 0.02) and CD80 (p = 0.03) in HBCs increased due to urban PM2.5 exposure. Urban PM2.5 showed detrimental effects on the placenta by disrupting tissue morphology and affecting HBC polarization specifically. These results extend the currently accepted view on properties of HBCs, by demonstrating their ability to react plastically and specifically to different exogenous stimuli.