Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia

Song Zhang, Paige Barker, Kimberley J. Botting, Claire T. Roberts, Christine M. McMillan, Isabella Caroline McMillen, Janna L. Morrison

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, and glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results in early restriction of placental growth and either the development of chronic fetal hypoxemia (PaO2≤17 mmHg) in late gestation or in compensatory placental growth and the maintenance of fetal normoxemia (PaO2>17 mmHg). Based on fetal PaO2, Cx, and Control ewes were assigned to either a normoxemic fetal group (Nx) or a hypoxemic fetal group (Hx) in late gestation, resulting in 4 groups. Cx resulted in a decrease in the volumes of fetal and maternal connective tissues in the placenta and increased placental mRNA expression of IGF2, vascular endothelial growth factor (VEGF), VEGFR-2, ANGPT2, and TIE2. There were reduced volumes of trophoblast, maternal epithelium, and maternal connective tissues in the placenta and a decrease in placental GLUT1 and 11bHSD2 mRNA expression in the Hx compared to Nx groups. Our data show that early restriction of placental growth has effects on morphological and functional characteristics of the placenta in late gestation, independent of whether the fetus becomes hypoxemic. Similarly, there is a distinct set of placental changes that are only present in fetuses that were hypoxemic in late gestation, independent of whether Cx occurred. Thus, we provide further understanding of the different placental cellular and molecular mechanisms that are present in early placental restriction and in the emergence of later placental insufficiency.

Original languageEnglish
Article numbere13049
JournalPhysiological Reports
Volume4
Issue number23
DOIs
Publication statusPublished - 6 Dec 2016
Externally publishedYes

Bibliographical note

ª2016 The Authors.Physiological Reportspublished by Wiley Periodicals, Inc. on behalf ofThe Physiological Society and the American Physiological Society.This is an open access article under the terms of the Creative Commons Attribution License,which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Keywords

  • Carunclectomy
  • Fetus
  • Hypoxemia
  • Intrauterine growth restriction
  • Placenta
  • Pregnancy

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