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17 January 2018 Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction
Karen J. Gibbins, Katherine N. Gibson-Corley, Ashley S. Brown, Matthew Wieben, Richard C. Law, Camille M. Fung
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Abstract

Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most common cause of fetal growth restriction (FGR) in the developed world. Despite the known negative consequences of HDP both to the mother and fetus, little is known about the longitudinal placental changes that occur as HDP progresses in pregnancy. This is because longitudinal sampling of human placentae during each gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog infusion to mimic human HDP in the last trimester, we calculated placental efficiencies based on fetal and placental weights; quantified spongiotrophoblast and labyrinth thicknesses and vascular density within these layers; examined whether hypoxia signaling pathway involving vascular endothelial growth factor A (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs) contributed to vascular change; and examined nutrient transporter abundance including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and 4 (FATP2, FATP4), and fatty acid translocase (CD36) from embryonic day 15.5 to 19 in a 20-day C57Bl/6J mouse gestation. We conclude that early-to-mid gestation hypertensive placentae show compensatory mechanisms to preserve fetal growth by increasing placental efficiencies and maintaining abundance of important nutrient transporters. As placental vascular network diminishes over late hypertension, placental efficiency diminishes and fetal growth fails. Neither hypoxia signaling pathway nor MMPs mediated the vascular diminution in thismodel. Hypertensive placentae surprisingly exhibit a sex-differential expression of nutrient transporters in late gestation despite showing fetal growth failure in both sexes.

Summary Sentence

Excess thromboxane A2 leads to a mouse phenotype of hypertensive disease of pregnancy and fetal growth restriction with evidence of altered placental vascular development and nutrient transporter abundance.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Karen J. Gibbins, Katherine N. Gibson-Corley, Ashley S. Brown, Matthew Wieben, Richard C. Law, and Camille M. Fung "Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction," Biology of Reproduction 98(5), 695-704, (17 January 2018). https://doi.org/10.1093/biolre/ioy006
Received: 14 June 2017; Accepted: 16 January 2018; Published: 17 January 2018
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