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Fetal programming and lactation: modulating gene expression in response to undernutrition during intrauterine life

Ignacio Monedero Cobeta1, Raquel Gomez Bris1,2, Pilar Rodríguez-Rodríguez1

  • 1Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, 28029, Madrid, Spain.

Pediatric Research
|February 7, 2024
PubMed

Insights

Maternal undernutrition during pregnancy can program the heart for disease. The lactation period offers a critical window to counteract these effects, mitigating cardiac hypertrophy by modulating gene expression.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Genetics

Background:

  • Fetal programming, resulting from adverse intrauterine conditions like maternal undernutrition, increases adult cardiometabolic disease risk.
  • Maternal undernutrition during gestation (MUN) is linked to low birth weight and subsequent health issues.

Purpose of the Study:

  • To investigate the impact of maternal undernutrition on cardiac gene expression and structure in a rat model.
  • To determine if the lactation period can mitigate the effects of fetal programming on cardiac health.

Main Methods:

  • Utilized a rat model of maternal undernutrition during gestation.
  • Employed RNA-sequencing and qPCR to analyze cardiac gene expression in offspring.
  • Assessed cardiac structure and function using transthoracic echocardiography and cross-fostering experiments.

Main Results:

  • Identified altered expression of cardiac genes, including Agt and Pparg, in offspring of undernourished mothers.
  • Observed increased Agt and decreased Pparg expression, correlating with cardiac hypertrophy in male offspring at birth.
  • Demonstrated that cross-fostering with control milk reduced cardiac hypertrophy and normalized gene expression in affected males.

Conclusions:

  • Fetal programming significantly alters cardiac gene expression, contributing to cardiac hypertrophy.
  • The lactation period is a critical window for intervention, capable of mitigating the detrimental effects of fetal programming on cardiac development.
  • Modulating gene expression of Agt and Pparg during lactation can prevent or reverse cardiac remodeling induced by early-life adversity.
Abstract

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