Uterine artery transcriptomic signatures of e-cigarette aerosol exposure in pregnancy

Electronic cigarette (e-cig) use among U.S. adults has shifted notably, with increased adoption among younger adults and middle-aged individuals transitioning from traditional cigarettes. We herein investigated the impact of gestational e-cig aerosol exposure on uterine artery (UA) transcriptome. Timed-pregnant Sprague-Dawley rats were randomly assigned to either the pair-fed Control or the E-cig group before initiation of vaping (4 s e-cig vapor every 2 min, two episodes of 1.5 h each; gestational day (GD) 5 until GD 20). Maternal weight and placental efficiency were not altered, whereas there was a significant deficit in fetal body weight and crown-rump length in the E-cig group on GD 21. Twenty three genes were significantly upregulated, while 40 genes were downregulated in the uterine artery of the E-cig group when compared with the Control group uterine artery. The top significantly downregulated genes in the uterine artery include genes involved in extracellular matrix and Wnt signaling regulation (Smoc2, Gpc3, Frzb, Sfrp2), immune and inflammatory response (C1qtTNF3, Tmem82, Clec21), muscle contraction (Actc1) and cell migration ( Gas2l3, Ret, Robo2). Top upregulated genes in the uterine artery (Vsig4, Agt, Cntn2, Kcnk5, Fhad1, Fgf13, Ctxn1, Prg4, and Pln) included genes involved in immune response and regulation (Vsig4, Kcnk5), and uterine artery vasodilation (Agt). Significant differences between the Control and E-cig groups were validated using Principal Component Analysis (PCA) and k-means clustering. These findings reveal how e-cig aerosol exposure during pregnancy may disrupt key biological processes in the uterine artery that delivers O₂ and nutrients to the fetoplacental compartment.