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Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

Thu N A Doan1,2, Jessica F Briffa3, Aaron L Phillips1

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

Journal of Developmental Origins of Health and Disease
|December 22, 2020
PubMed

Insights

Intrauterine growth restriction (IUGR) in rats leads to kidney problems and high blood pressure, with epigenetic changes potentially explaining sex-specific effects and transmission across generations. These changes in gene expression may impact kidney development and function.

Area of Science:

  • Reproductive biology
  • Developmental biology
  • Epigenetics

Background:

  • Intrauterine growth restriction (IUGR) impairs fetal development due to placental insufficiency.
  • IUGR offspring face increased risks of hypertension and chronic kidney disease later in life.
  • In rats, IUGR causes nephron deficits, with males exhibiting kidney dysfunction and hypertension, and these effects can transmit across generations.

Purpose of the Study:

  • To investigate the role of epigenetic mechanisms in sex-specific programming and transgenerational transmission of IUGR-related kidney phenotypes.
  • To examine the expression of DNA methyltransferases and imprinted genes in the kidneys of IUGR rats across generations.

Main Methods:

  • Kidney tissues from sham and IUGR rats (F1 and F2 generations) were analyzed for gene expression.
  • Expression levels of DNA methyltransferases (Dnmt1, Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, Cdkn1c) were quantified.
  • Analyses included embryonic day 20, postnatal day 1, and 6- and 12-month-old offspring from paternal and maternal lines.

Main Results:

  • IUGR rats showed decreased Dnmt3a expression at E20 and altered Cdkn1c and Kcnq1 expression at PN1 compared to controls.
  • Sex-specific differences in Cdkn1c and Snrpn expression were observed in E20 IUGR males versus females.
  • Loss of Peg3 sex-specific expression occurred in F2 IUGR offspring from the maternal line.

Conclusions:

  • Epigenetic alterations in kidney development may occur in IUGR offspring.
  • These epigenetic changes could contribute to altered kidney function and predisposition to kidney disease.
  • Findings suggest a potential mechanism for sex-specific programming and multigenerational effects of IUGR.

Keywords:
Intrauterine growth restrictionfetal developmentimprinted geneskidneyuteroplacental insufficiency

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