Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction

Research output: Contribution to journalArticle

Authors

  • Sydney L. Lane
  • Alexandrea S. Doyle
  • Elise S. Bales
  • Ramón A. Lorca
  • Colleen G. Julian
  • Lorna G. Moore

External Institution(s)

  • University of Colorado Denver

Details

Original languageEnglish (US)
Pages (from-to)660-670
Number of pages11
JournalBiology of reproduction
Volume102
Issue number3
StatusPublished - Mar 13 2020
Peer-reviewedYes

Abstract

Incomplete maternal vascular responses to pregnancy contribute to pregnancy complications including intrauterine growth restriction (IUGR) and preeclampsia. We aimed to characterize maternal vascular dysfunction in a murine model of fetal growth restriction as an approach toward identifying targetable pathways for improving pregnancy outcomes. We utilized a murine model of late-gestation hypoxia-induced IUGR that reduced E18.5 fetal weight by 34%. Contrary to our hypothesis, uterine artery blood flow as measured in vivo by Doppler ultrasound was increased in mice housed under hypobaric hypoxia (385 mmHg; 5500 m) vs normoxia (760 mmHg; 0 m). Using wire myography, uterine arteries isolated from hypoxic mice had similar vasodilator responses to the two activators A769662 and acetylcholine as those from normoxic mice, although the contribution of an increase in nitric oxide production to uterine artery vasodilation was reduced in the hypoxic vs normoxic groups. Vasoconstrictor responses to phenylephrine and potassium chloride were unaltered by hypoxia. The levels of activated adenosine monophosphate-activated protein kinase (AMPK) were reduced with hypoxia in both the uterine artery and placenta as measured by western blot and immunohistochemistry. We concluded that the rise in uterine artery blood flow may be compensatory to hypoxia but was not sufficient to prevent fetal growth restriction. Although AMPK signaling was reduced by hypoxia, AMPK was still receptive to pharmacologic activation in the uterine arteries in which it was a potent vasodilator. Thus, AMPK activation may represent a new therapy for pregnancy complications involving reduced uteroplacental perfusion.

    Research areas

  • hypoxia, IUGR, pregnancy, uterine artery

Citation formats

APA

Lane, S. L., Doyle, A. S., Bales, E. S., Lorca, R. A., Julian, C. G., & Moore, L. G. (2020). Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction. Biology of reproduction, 102(3), 660-670. https://doi.org/10.1093/biolre/ioz208

Harvard

Lane, SL, Doyle, AS, Bales, ES, Lorca, RA, Julian, CG & Moore, LG 2020, 'Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction', Biology of reproduction, vol. 102, no. 3, pp. 660-670. https://doi.org/10.1093/biolre/ioz208