title: Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes.
abstract: Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of the condition, with ∼50% of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied whether placental vascularity, angiogenesis and glucose transport reflect FGR severity.
  
  
  
  Singleton pregnancies were established in adolescent ewes either overnourished to putatively restrict fetoplacental growth (n = 27) or control-fed (n = 12). At 131d (term = 145d) pregnancies were interrupted and fetuses classified as FGR (n = 17, <4222 g, -2SD below control-fed mean) or non-FGR (n = 10). Placentome capillary area density (CAD), number density (CND), surface density (CSD), and area per capillary (APC) in the fetal cotyledon (COT) and maternal caruncle (CAR) were analysed using immunostaining. COT/CAR mRNA expression of angiogenic ligands/receptors and glucose transporters were measured by qRT-PCR.
  
  
  
  Fetal weight was reduced in FGR vs. Non-FGR/Control groups. Total placentome weight was Control > Non-FGR > FGR and fetal:placental weight ratios were higher in overnourished versus Control groups. COT vascular indices were Non-FGR > FGR > Control. COT-CAD, CSD and APC were significantly greater in Non-FGR overnourished versus Control and intermediate in FGR groups. CAR vascularity did not differ. CAR-VEGFA/FLT1/KDR/ANGPT1/ANGPT2/SLC2A1/SLC2A3 mRNA was lower and COT-ANGPT2 higher in overnourished versus Control groups.
  
  
  
  Relative to control-intake pregnancy, overnourished pregnancies are characterised by higher COT vascularity, potentially a compensatory response to reduced nutrient supply, reflected by higher fetal:placental weight ratios. Compared with overnourished pregnancies where fetal growth is relatively preserved, overnourished pregnancies culminating in marked FGR have less placental vascularity, suggesting incomplete adaptation to the prenatal insult.
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK; UCL Institute for Women's Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK. Electronic address: davidcarr@doctors.org.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Carr
authors.affiliation: UCL Institute for Women's Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: David
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK.
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Aitken
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Milne
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND, 58108, USA.
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Borowicz
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Wallace
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND, 58108, USA.
authors.forename: Dale A
authors.initials: DA
authors.lastname: Redmer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D012756:Sheep; D016216:Ultrasonography, Prenatal
chemical_list: D015415:Biomarkers
keywords: Angiogenic factors; Angiopoietin; Fetal growth restriction; Placental vascularity; Sheep