title: Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia.
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 11βHSD2 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.
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Paige
authors.initials: P
authors.lastname: Barker
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Kimberley J
authors.initials: KJ
authors.lastname: Botting
authors.affiliation: The Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Roberts
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Christine M
authors.initials: CM
authors.lastname: McMillan
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Isabella Caroline
authors.initials: IC
authors.lastname: McMillen
authors.affiliation: Early Origins of Adult Health Research Group, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia Janna.Morrison@unisa.edu.au.
authors.forename: Janna L
authors.identifier: 0000-0002-8602-8519
authors.initials: JL
authors.lastname: Morrison
mesh_terms: D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D010927:Placental Insufficiency / Q000378:metabolism* / Q000473:pathology; D010929:Placentation; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D007335:Insulin-Like Growth Factor II; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Carunclectomy; fetus; hypoxemia; intrauterine growth restriction; placenta; pregnancy