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Epigenetic Mechanisms Responsible for the Transgenerational Inheritance of Intrauterine Growth Restriction Phenotypes

Thu Ngoc Anh Doan1,2, Lisa K Akison3, Tina Bianco-Miotto1,2

  • 1School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, Australia.

Frontiers in Endocrinology
|April 18, 2022
PubMed

Insights

Poor placental function causes fetal growth restriction, increasing offspring risk for chronic diseases like diabetes and hypertension. These conditions show sex-dependent inheritance and are linked to epigenetic changes.

Area of Science:

  • Reproductive Biology
  • Developmental Biology
  • Epigenetics

Background:

  • Placental insufficiency impairs fetal development, leading to fetal growth restriction (FGR).
  • FGR is associated with increased risk of chronic diseases in adulthood, including type-2 diabetes, hypertension, and kidney disease.
  • Evidence suggests FGR phenotypes and associated health risks can be transmitted across generations.

Purpose of the Study:

  • To review the long-term health outcomes for offspring experiencing fetal growth restriction.
  • To discuss the intergenerational transmission patterns of diseases linked to FGR.
  • To examine the role of epigenetic mechanisms in the transmission of FGR-related phenotypes.

Main Methods:

  • Literature review of animal studies and human observational data.
  • Analysis of research on placental function and fetal development.
  • Examination of studies investigating epigenetic modifications (DNA methylation, histone modifications, non-coding RNAs) in FGR.

Main Results:

  • Fetal growth restriction is linked to sex-dependent health outcomes in offspring.
  • Transgenerational inheritance of FGR-related chronic disease risk has been observed through both maternal and paternal lines.
  • Altered epigenetic mechanisms are associated with the transmission patterns of FGR phenotypes.

Conclusions:

  • Fetal growth restriction has significant, lasting health consequences for offspring.
  • Epigenetic dysregulation plays a crucial role in the inheritance of FGR-associated diseases.
  • Understanding these mechanisms is vital for developing preventative strategies against chronic diseases originating in utero.

Keywords:
cardiometabolic diseaseepigenetic mechanismsintrauterine growth restrictionkidney dysfunctionsmall for gestational agetransgenerational transmissionuteroplacental insufficiency

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