Cited by 117Congenital heart defects researchPregnancy and preeclampsia studiesBirth, Development, and Health

Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes

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Louey, Samantha, Jonker, Sonnet S., Giraud, George D., Thornburg, Kent L.·2007·The Journal of Physiology

Abstract

Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 ± 1 days (10 day group) or 136 ± 1 days (20 day group) of gestation (term ∼145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki‐67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: −21%, P < 0.05; 20 days: −27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by ∼70% (P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 ± 12.0 versus 46.0 ± 6.6%, P < 0.05; right ventricle: 29.4 ± 12.3 versus 46.3 ± 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes.

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Crossref · 10.1113/jphysiol.2006.122200

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  • A growth-restricted fetus has smaller coronary arteries, fewer but more immature cardiomyocytes, less elastin in the arteries, and fewer nephrons in the kidney.

    “For example, a growth-restricted fetus has smaller coronary arteries (288), fewer but more immature cardiomyocytes (55,348,394), less elastin in the arteries (152, 362, 526), and fewer nephrons in the kidney (22,352).”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [348]

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Authors
Louey, S., Jonker, S. S., Giraud, G. D., & Thornburg, K. L.
Affiliations
Oregon Health & Science University (US)
Venue
The Journal of Physiology
Publisher
Wiley
Published
2007-04-10
Volume
580
Issue
2
Pages
639-648
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W1563359662
Cited by
116
References
34
Citations by year
2026: 2 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 8
FWCI
1.72
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD034430, P01-HD-34430)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
placental insufficiency, fetal sheep, cardiomyocyte maturation, cardiomyocyte proliferation, cell cycle activity, Ki-67, fetal hypoxaemia, fetal heart development
MeSH terms
Animals, Cell Cycle, Cell Differentiation, Female, Fetus, Placental Insufficiency, Pregnancy, Sheep, Myocytes, Cardiac, Fetal Development

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