PMID- 29604078
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20191022
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 596
IP  - 12
DP  - 2018 Jun
TI  - Maternal undernutrition in late gestation increases IGF2 signalling molecules and 
      collagen deposition in the right ventricle of the fetal sheep heart.
PG  - 2345-2358
LID - 10.1113/JP275806 [doi]
AB  - KEY POINTS: This study investigates the impact of decreased fetal plasma glucose 
      concentrations on the developing heart in late gestation, by subjecting pregnant 
      ewes to a 50% global nutrient restriction. Late gestation undernutrition (LGUN) 
      decreased fetal plasma glucose concentrations whilst maintaining a normoxemic 
      blood gas status. LGUN increased the mRNA expression of IGF2 and IGF2R. Fetal 
      plasma glucose concentrations, but not fetal blood pressure, were significantly 
      correlated with IGF2 expression and the activation of CAMKII in the fetal right 
      ventricle. LGUN increased interstitial collagen deposition and altered the 
      protein abundance of phospho-PLB and phospho-troponin I, regulators of cardiac 
      contractility and relaxation. This study shows that a decrease in fetal plasma 
      glucose concentrations may play a role in the development of detrimental changes 
      in the right ventricle in early life, highlighting CAMKII as a potential target 
      for the development of intervention strategies. ABSTRACT: Exposure of the fetus 
      to a range of environmental stressors, including maternal undernutrition, is 
      associated with an increased risk of death from cardiovascular disease in adult 
      life. This study aimed to determine the effect of maternal nutrient restriction 
      in late gestation on the molecular mechanisms that regulate cardiac growth and 
      development of the fetal heart. Maternal undernutrition resulted in a decrease in 
      fetal glucose concentrations across late gestation, whilst fetal arterial PO2 
      remained unchanged between the control and late gestation undernutrition (LGUN) 
      groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through 
      the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an 
      increase in hypertrophic signalling. LGUN also resulted in an increased mRNA 
      expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. 
      In addition, there was an inverse relationship between fetal glucose 
      concentrations and COL1A expression. The presence of interstitial fibrosis in the 
      heart of the LGUN group was confirmed through the quantification of picrosirius 
      red-stained sections of the right ventricle. We have therefore shown that 
      maternal undernutrition in late gestation may drive the onset of myocardial 
      remodelling in the fetal right ventricle and thus has negative implications for 
      right ventricle function and cardiac health in later life.
CI  - (c) 2018 The Authors. The Journal of Physiology (c) 2018 The Physiological Society.
FAU - Darby, Jack R T
AU  - Darby JRT
AUID- ORCID: 0000-0001-7114-3920
AD  - Early Origins of Adult Health Research Group, School of Pharmacy & Medical 
      Sciences, Sansom Institute for Health Research, University of South Australia, 
      Adelaide, SA, 5001, Australia.
FAU - McMillen, I Caroline
AU  - McMillen IC
AD  - Early Origins of Adult Health Research Group, School of Pharmacy & Medical 
      Sciences, Sansom Institute for Health Research, University of South Australia, 
      Adelaide, SA, 5001, Australia.
FAU - Morrison, Janna L
AU  - Morrison JL
AUID- ORCID: 0000-0002-8602-8519
AD  - Early Origins of Adult Health Research Group, School of Pharmacy & Medical 
      Sciences, Sansom Institute for Health Research, University of South Australia, 
      Adelaide, SA, 5001, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180520
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - 9007-34-5 (Collagen)
SB  - IM
CIN - J Physiol. 2018 Jun;596(12):2279-2280. PMID: 29676799
MH  - Animals
MH  - Collagen/*metabolism
MH  - Female
MH  - Fetal Diseases/etiology/*physiopathology
MH  - Fetal Heart/metabolism/*physiopathology
MH  - Fibrosis/etiology/physiopathology
MH  - Gestational Age
MH  - Heart Ventricles/metabolism/physiopathology
MH  - Insulin-Like Growth Factor II/metabolism
MH  - Malnutrition/*complications/metabolism
MH  - Maternal Nutritional Physiological Phenomena
MH  - Maternal-Fetal Exchange
MH  - Pregnancy
MH  - Sheep
MH  - Sheep Diseases/*physiopathology
MH  - *Signal Transduction
PMC - PMC6002234
OTO - NOTNLM
OT  - IGF2
OT  - cardiac
OT  - fetus
OT  - fibrosis
OT  - heart
OT  - signalling
OT  - undernutrition
EDAT- 2018/04/01 06:00
MHDA- 2019/10/23 06:00
PMCR- 2019/06/15
CRDT- 2018/04/01 06:00
PHST- 2018/01/23 00:00 [received]
PHST- 2018/03/26 00:00 [accepted]
PHST- 2018/04/01 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/04/01 06:00 [entrez]
PHST- 2019/06/15 00:00 [pmc-release]
AID - TJP12948 [pii]
AID - 10.1113/JP275806 [doi]
PST - ppublish
SO  - J Physiol. 2018 Jun;596(12):2345-2358. doi: 10.1113/JP275806. Epub 2018 May 20.