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Updated: May 24, 2026
Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the
M Jane Black1, Andrew L Siebel, Oksan Gezmish
1Dept. of Anatomy & Developmental Biology, Monash Univ., Clayton, Victoria, Australia. jane.black@monash.edu
Insights
Early life growth restriction can reduce heart cell number, leading to lifelong cardiac issues. However, improved neonatal nutrition can restore cardiomyocyte numbers, preventing hypertension later in life.
Area of Science:
- Developmental biology
- Cardiovascular science
- Neonatal nutrition
Background:
- Reduced cardiomyocyte numbers in early life can impair lifelong cardiac function.
- Prenatal and postnatal environments play a role in programming cardiomyocyte growth.
Purpose of the Study:
- To investigate the impact of prenatal and postnatal growth restriction on cardiomyocyte development using a rat cross-fostering model.
- To determine if improved postnatal nutrition can mitigate the adverse effects of early life growth restriction on cardiomyocyte number and cardiac function.
Main Methods:
- Rat dams underwent uterine vessel ligation (Restricted) or sham surgery (Control) during gestation.
- Offspring were cross-fostered to mothers with normal (Control) or impaired (Restricted) lactation.
- Gene expression, cardiomyocyte number (stereology), blood pressure, and cardiac gene expression were assessed at various developmental time points.
Main Results:
- Prenatal restriction increased Igf1 and Igf2 mRNA. Postnatal growth restriction elevated Agtr1a, Agtr1b, Bcl2, and Cmyc mRNA.
- A significant reduction in cardiomyocyte number was observed in the Restricted-on-Restricted group (-29%).
- Improved postnatal nutrition (Restricted-on-Control) prevented the cardiomyocyte deficit and subsequent hypertension at 6 months.
Conclusions:
- A critical developmental window exists where cardiomyocytes are still proliferating.
- Optimized neonatal nutrition can restore cardiomyocyte number to normal levels, preventing long-term cardiac dysfunction.
- Findings are highly relevant to preterm infants with immature cardiomyocytes.
Abstract:
A reduced complement of cardiomyocytes in early life can adversely affect life-long cardiac functional reserve. In the present study, using a cross-fostering approach in rats, we examined the contributions of the prenatal and postnatal environments in the programming of cardiomyocyte growth. Rat dams underwent either bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation. One day after birth, Control and Restricted pups were cross-fostered onto Control (normal lactation) or Restricted (impaired lactation due to impaired mammary gland formation) mothers. In male offspring, genes involved in cardiomyocyte differentiation, proliferation, hypertrophy and apoptosis were examined at gestational day 20 and postnatal days 1 and 7 to assess effects on cardiomyocyte growth. At postnatal day 7 cardiomyocyte number was determined stereologically. Offspring were examined at age 6 mo for evidence of hypertension and pathological cardiac gene expression. There was an increase in Igf1 and Igf2 mRNA expression in hearts of Restricted pups at gestational day 20. At postnatal day 7, Agtr1a and Agtr1b mRNA expression as well as Bcl2 and Cmyc were elevated in all hearts from offspring that were prenatally or postnatally growth restricted. There was a significant reduction (-29%) in cardiomyocyte number in the Restricted-on-Restricted group. Importantly, this deficit was prevented by optimization of postnatal nutrition (in the Restricted-on-Control group). At 6 mo, blood pressure was significantly elevated in the Restricted-on-Restricted group, but there was no difference in expression of the cardiac hypertrophy, remodeling or angiogenic genes across groups. In conclusion, the findings reveal a critical developmental window, when cardiomyocytes are still proliferating, whereby improved neonatal nutrition has the capacity to restore cardiomyocyte number to normal levels. These findings are of particular relevance to the preterm infant who is born at a time when cardiomyocytes are immature and still dividing.
