The lifelong impact of fetal growth restriction on cardiac development

Emily P. Masoumy, Alexandra A. Sawyer, Suash Sharma, Jenny A. Patel, Paul M.K. Gordon, Timothy R.H. Regnault, Brad Matushewski, Neal Lee Weintraub, Bryan Richardson, Jennifer A. Thompson, Brian Kevin Stansfield

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Maternal nutrient restriction (MNR) is a widespread cause of fetal growth restriction (FGR), an independent predictor of heart disease and cardiovascular mortality. Our objective was to examine the developmental and long-term impact of MNR-induced FGR on cardiac structure in a model that closely mimics human development. Methods: A reduction in total caloric intake spanning pregestation through to lactation in guinea pig sows was used to induce FGR. Proliferation, differentiation, and apoptosis of cardiomyocytes were assessed in late-gestation fetal, neonatal, and adult guinea pig hearts. Proteomic analysis and pathway enrichment were performed on fetal hearts. Results: Cardiomyocyte proliferation and the number of mononucleated cells were enhanced in the MNR–FGR fetal and neonatal heart, suggesting a delay in cardiomyocyte differentiation. In fetal hearts of MNR–FGR animals, apoptosis was markedly elevated and the total number of cardiomyocytes reduced, the latter remaining so throughout neonatal and into adult life. A reduction in total cardiomyocyte number in adult MNR–FGR hearts was accompanied by exaggerated hypertrophy and a disorganized architecture. Pathway analysis identified genes related to cell proliferation, differentiation, and survival. Conclusions: FGR influences cardiomyocyte development during critical windows of development, leading to a permanent deficiency in cardiomyocyte number and compensatory hypertrophy in a rodent model that recapitulates human development.

Original languageEnglish (US)
Pages (from-to)537-544
Number of pages8
JournalPediatric Research
Volume84
Issue number4
DOIs
StatePublished - Oct 1 2018

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Fetal Development
Cardiac Myocytes
Fetal Heart
Human Development
Hypertrophy
Guinea Pigs
Mothers
Apoptosis
Food
Energy Intake
Lactation
Proteomics
Cell Differentiation
Rodentia
Heart Diseases
Cell Survival
Cell Count
Cell Proliferation
Pregnancy
Mortality

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Masoumy, E. P., Sawyer, A. A., Sharma, S., Patel, J. A., Gordon, P. M. K., Regnault, T. R. H., ... Stansfield, B. K. (2018). The lifelong impact of fetal growth restriction on cardiac development. Pediatric Research, 84(4), 537-544. https://doi.org/10.1038/s41390-018-0069-x

The lifelong impact of fetal growth restriction on cardiac development. / Masoumy, Emily P.; Sawyer, Alexandra A.; Sharma, Suash; Patel, Jenny A.; Gordon, Paul M.K.; Regnault, Timothy R.H.; Matushewski, Brad; Weintraub, Neal Lee; Richardson, Bryan; Thompson, Jennifer A.; Stansfield, Brian Kevin.

In: Pediatric Research, Vol. 84, No. 4, 01.10.2018, p. 537-544.

Research output: Contribution to journalArticle

Masoumy, EP, Sawyer, AA, Sharma, S, Patel, JA, Gordon, PMK, Regnault, TRH, Matushewski, B, Weintraub, NL, Richardson, B, Thompson, JA & Stansfield, BK 2018, 'The lifelong impact of fetal growth restriction on cardiac development', Pediatric Research, vol. 84, no. 4, pp. 537-544. https://doi.org/10.1038/s41390-018-0069-x
Masoumy EP, Sawyer AA, Sharma S, Patel JA, Gordon PMK, Regnault TRH et al. The lifelong impact of fetal growth restriction on cardiac development. Pediatric Research. 2018 Oct 1;84(4):537-544. https://doi.org/10.1038/s41390-018-0069-x
Masoumy, Emily P. ; Sawyer, Alexandra A. ; Sharma, Suash ; Patel, Jenny A. ; Gordon, Paul M.K. ; Regnault, Timothy R.H. ; Matushewski, Brad ; Weintraub, Neal Lee ; Richardson, Bryan ; Thompson, Jennifer A. ; Stansfield, Brian Kevin. / The lifelong impact of fetal growth restriction on cardiac development. In: Pediatric Research. 2018 ; Vol. 84, No. 4. pp. 537-544.
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