Vaping in Pregnancy: Unraveling Molecular Drivers of Preeclampsia and Fetal Growth Restriction

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major pregnancy complications that are linked to placental dysfunction and environmental stimulation such as the use of electronic cigarettes (eCig). This study investigates the molecular impacts of timed eCig exposure in a C57BL/6 mouse model of PE and IUGR using bulk RNA-sequencing of placental tissues. Pregnant mice were exposed to eCig vapor via nose-only system starting at embryonic day 12.5 (eCig-6d, before spiral artery (SA) invasion) or 14.5 (eCig-4d, after SA invasion) until E18.5 (necropsy), with healthy controls exposed to room air (<i>n</i> = 6/group). The eCig-4d group developed PE, whereas the eCig-6d group developed both PE and IUGR. RNA-seq analysis revealed 429 differentially expressed genes (DEGs) in eCig-4d (IUGR-like) group and 64 DEGs in eCig-6d (PE + IUGR-like) group compared to controls. Pathway and gene network analyses indicated that eCig-4d exposure activated NF-κB-driven inflammation, suppressed ECM organization and collagen biosynthesis, and downregulated vasoactive genes/mitochondrial-associated genes (<i>NOS1/2</i>), accompanied by impaired complement initiation and reduced both macrophage and monocyte signals. Similarly, eCig-6d exposure led to downregulation of complement-associated genes and granule-related components, possibly implicating weakened neutrophil responsiveness and compromised inflammatory resolution at the maternal-fetal interface. Our findings align with prior studies on physiological dysfunctions in PE and IUGR, while also providing novel insights into the temporally specific cellular responses induced by eCig exposure.