Regulator of G Protein Signaling 2 Facilitates Uterine Artery Adaptation During Pregnancy in Mice

BACKGROUND: Decreased uterine blood flow is known to contribute to pregnancy complications such as gestational hypertension and preeclampsia. Previously, we showed that the loss of regulator of G protein signaling 2 (RGS2), a GTPase activating protein for G(q/11) and G(i/o) class G proteins, decreases uterine blood flow in the nonpregnant state in mice. Here, we examined the effects of the absence of RGS2 and 5 on uterine blood flow and uterine vascular structure and function at early, mid, and late gestation, as well as peripartum period in mice. METHODS AND RESULTS: Abdominal Doppler ultrasonography was performed on adult female wild‐type, Rgs2(−/−), and Rgs5(−/−) mice at pre‐pregnancy, gestational days 10, 15, and 18, and postpartum day 3. Uterine artery structure and function were also assessed by vessel myograph studies. At mid‐pregnancy, uterine blood flow decreased in both Rgs2(−/−) and Rgs5(−/−) mice, whereas resistive index increased only in Rgs2(−/−) mice. In uterine arteries from wild‐type mice, mRNA expression of RGS2 and 4 increased, whereas RGS5 expression remained elevated at mid‐pregnancy. These changes in gene expression were unique to uterine arteries because they were absent in mesenteric arteries and the aorta of wild‐type mice. In Rgs2(−/−) mice, uterine artery medial cross‐sectional area and G protein–coupled receptor‐mediated vasoconstriction increased in mid‐pregnancy, implicating a role for RGS2 in structural and functional remodeling of uterine arteries during pregnancy. In contrast, RGS5 absence increased vasoconstriction only in the peripartum period. CONCLUSIONS: These data together indicate that RGS2 plays a critical role in the structural and functional remodeling of uterine arteries to impact uterine blood flow during pregnancy. Targeting the signaling pathway regulated by RGS2 may therefore be a therapeutic strategy for ameliorating utero‐placental perfusion disorders during pregnancy.