Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes

David J. Carr, Anna L. David, Raymond P. Aitken, John S. Milne, Pawel P. Borowicz, Jacqueline M. Wallace, Dale A. Redmer

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Abstract

Introduction Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of FGR, with ∼50% of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied if placental vascularity, angiogenesis and glucose transport reflected FGR severity. 
MethodsSingleton 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.
ResultsFetal 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. 
DiscussionRelative 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.
Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalPlacenta
Volume46
Early online date19 Aug 2016
DOIs
Publication statusPublished - Oct 2016

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Fetal Development
Growth
Pregnancy
Fetal Weight
Control Groups
Blood Vessels
Fetus
Glucose
Food
Messenger RNA

Keywords

  • Placental vascularity
  • Fetal growth restriction
  • Angiogenic factors
  • Sheep
  • Angiopoietin

Cite this

Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes. / Carr, David J.; David, Anna L.; Aitken, Raymond P.; Milne, John S.; Borowicz, Pawel P.; Wallace, Jacqueline M.; Redmer, Dale A.

In: Placenta, Vol. 46, 10.2016, p. 79-86.

Research output: Contribution to journalArticle

Carr, David J. ; David, Anna L. ; Aitken, Raymond P. ; Milne, John S. ; Borowicz, Pawel P. ; Wallace, Jacqueline M. ; Redmer, Dale A. / Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes. In: Placenta. 2016 ; Vol. 46. pp. 79-86.
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abstract = "Introduction Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of FGR, with ∼50{\%} of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied if placental vascularity, angiogenesis and glucose transport reflected FGR severity. MethodsSingleton 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.ResultsFetal 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. DiscussionRelative 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.",
keywords = "Placental vascularity, Fetal growth restriction, Angiogenic factors, Sheep, Angiopoietin",
author = "Carr, {David J.} and David, {Anna L.} and Aitken, {Raymond P.} and Milne, {John S.} and Borowicz, {Pawel P.} and Wallace, {Jacqueline M.} and Redmer, {Dale A.}",
note = "Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR).",
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T1 - Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes

AU - Carr, David J.

AU - David, Anna L.

AU - Aitken, Raymond P.

AU - Milne, John S.

AU - Borowicz, Pawel P.

AU - Wallace, Jacqueline M.

AU - Redmer, Dale A.

N1 - Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR).

PY - 2016/10

Y1 - 2016/10

N2 - Introduction Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of FGR, with ∼50% of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied if placental vascularity, angiogenesis and glucose transport reflected FGR severity. MethodsSingleton 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.ResultsFetal 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. DiscussionRelative 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.

AB - Introduction Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of FGR, with ∼50% of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied if placental vascularity, angiogenesis and glucose transport reflected FGR severity. MethodsSingleton 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.ResultsFetal 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. DiscussionRelative 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.

KW - Placental vascularity

KW - Fetal growth restriction

KW - Angiogenic factors

KW - Sheep

KW - Angiopoietin

U2 - 10.1016/j.placenta.2016.08.076

DO - 10.1016/j.placenta.2016.08.076

M3 - Article

VL - 46

SP - 79

EP - 86

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -