The epidermal growth factor receptor in healthy pregnancy and preeclampsia

Abstract

The epidermal growth factor receptor (EGFR) is expressed robustly in the placenta, and critical processes of pregnancy such as placental growth and trophoblast fusion are dependent on EGFR function. However, the role that aberrant EGFR signaling might play in the etiology and/or maintenance of preeclampsia (PE) remains largely unexplored. Recently, we have shown that overexpression of EGFR in cultured uterine artery endothelial cells (UAEC), which express little endogenous EGFR, remaps responsiveness away from vascular endothelial growth factor receptor (VEGFR) signaling and towards EGFR, suggesting that endothelial EGFR expression may be kept low to prevent interference with VEGFR control of angiogenesis. Here we will consider evidence for the possibility that the endothelial dysfunction observed in PE might in some cases result from elevation of endothelial EGFR. During pregnancy, trophoblasts are known to synthesize large amounts of EGFR protein, and the placenta regularly releases syncytiotrophoblast (STB)-derived exosomes and microparticles into the maternal circulation. Although there are no reports of elevated Egfr gene expression in preeclamptic endothelial cells, the ongoing shedding of placental vesicles into the vascular system raises the possibility that EGFR-rich vesicles might be taken up by the endothelium, thereby contributing to the symptoms of PE by interrupting angiogenesis and blocking pregnancy adapted vasodilatory function.

Uterine macrophages and NK cells exhibit population and gene-level changes after implantation but maintain pro-invasive properties

“…We found that each macrophage subtype was rich in transcripts encoding cytokines, chemokines, and growth factors that could plausibly promote EVT invasion or otherwise signal to fetal trophoblasts. AREG and EREG signal to EGFR, which has been shown in several studies to regulate normal and adverse outcomes of pregnancy, as has VEGF ( 89 , 90 ). GPNMB promotes proliferation, invasion and metastasis of tumor cells ( 70 ).…”