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

Published online by Cambridge University Press:  22 December 2020

Thu N. A. Doan ,
Jessica F. Briffa ,
Aaron L. Phillips ,
Shalem Y. Leemaqz ,
Rachel A. Burton ,
Tania Romano Open the ORCID record for Tania Romano [Opens in a new window] ,
Mary E. Wlodek  and
Tina Bianco-Miotto Open the ORCID record for Tina Bianco-Miotto [Opens in a new window]
Thu N. A. Doan
Affiliation:
School of Agriculture, Food and Wine & Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia Robinson Research Institute, University of Adelaide, South Australia, Australia
Jessica F. Briffa
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
Aaron L. Phillips
Affiliation:
School of Agriculture, Food and Wine & Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia
Shalem Y. Leemaqz
Affiliation:
Robinson Research Institute, University of Adelaide, South Australia, Australia South Australian Health & Medical Research Institute, SAHMRI Women and Kids, Adelaide, Australia College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
Rachel A. Burton
Affiliation:
School of Agriculture, Food and Wine & Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia
Tania Romano
Affiliation:
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria, Australia
Mary E. Wlodek
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
Tina Bianco-Miotto*
Affiliation:
School of Agriculture, Food and Wine & Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia Robinson Research Institute, University of Adelaide, South Australia, Australia
*
Address for correspondence:*Tina Bianco-Miotto, School of Agriculture, Food and Wine & Waite Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Email: tina.bianco@adelaide.edu.au
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Abstract

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

Keywords

Intrauterine growth restrictionuteroplacental insufficiencykidneyfetal developmentimprinted genes
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 6 , December 2021 , pp. 952 - 962
Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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