Citation

Overview: Uterine vascular adaptations to pregnancy facilitate rises in blood flow
to supply nutrients and oxygen to the developing fetus. Preeclampsia (PE) and
intrauterine growth restriction (IUGR) are associated with aberrant uterine
adaptation resulting from endothelial cell dysfunction. Estradiol-17β (E2β) mediates
uterine vascular adaptations, such as vasodilation and angiogenesis, which are
facilitated in part by uterine artery endothelial cells (UAECs). We recently
demonstrated that catecholestradiols (2-OHE2, 4-OHE2) and methoxyestradiols (4-
ME2, and/or 2-ME2) also regulate processes of angiogenesis and vasodilation via
ER-independent mechanisms. In addition, pregnancy-specific programming (PSP)
of UAECs plays a role in the pregnancy-specific effects of E2β and its metabolites
in vitro. However, the mechanisms mediating the effects of E2β and its metabolites
on UAECs, as well as PSP have not been determined. We hypothesize that the
mechanisms mediating angiogenesis and vasodilation induced by E2β and its
metabolites are similar and unique to the pregnant uterine environment. We also
hypothesize that PSP of UAECs is driven by the local gravid uterine environment
directly adjacent uterine arteries.