Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy

• Published in: International journal of molecular sciences 2020-06, Vol.21 (12), p.4349
• Main Authors: Bai, Jin, Qi, Qian-Rong, Li, Yan, Day, Robert, Makhoul, Josh, Magness, Ronald R, Chen, Dong-Bao
• Format: Article
• Language: English
• Subjects: Biosynthesis; Blood flow; Blood pressure; Endothelial cells; Epigenesis, Genetic; Estrogen receptors; Estrogens; Estrogens - metabolism; Female; Fetuses; Heart rate; Hemodynamics; Humans; Hydrogen sulfide; Kinases; Ligands; Literature reviews; Muscles; Nitric oxide; Nitric Oxide - metabolism; Ovaries; Physiology; Preeclampsia; Pregnancy; Proteins; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Reproductive system; Review; Sheep; Smooth muscle; uterine artery; Uterine Artery - metabolism; Uterine Artery - pathology; Uterus; vasodilatation; Vasodilation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21124349

Normal pregnancy is associated with dramatic increases in uterine blood flow to facilitate the bidirectional maternal-fetal exchanges of respiratory gases and to provide sole nutrient support for fetal growth and survival. The mechanism(s) underlying pregnancy-associated uterine vasodilation remain incompletely understood, but this is associated with elevated estrogens, which stimulate specific estrogen receptor (ER)-dependent vasodilator production in the uterine artery (UA). The classical ERs (ERα and ERβ) and the plasma-bound G protein-coupled ER (GPR30/GPER) are expressed in UA endothelial cells and smooth muscle cells, mediating the vasodilatory effects of estrogens through genomic and/or nongenomic pathways that are likely epigenetically modified. The activation of these three ERs by estrogens enhances the endothelial production of nitric oxide (NO), which has been shown to play a key role in uterine vasodilation during pregnancy. However, the local blockade of NO biosynthesis only partially attenuates estrogen-induced and pregnancy-associated uterine vasodilation, suggesting that mechanisms other than NO exist to mediate uterine vasodilation. In this review, we summarize the literature on the role of NO in ER-mediated mechanisms controlling estrogen-induced and pregnancy-associated uterine vasodilation and our recent work on a "new" UA vasodilator hydrogen sulfide (H S) that has dramatically changed our view of how estrogens regulate uterine vasodilation in pregnancy.