Impact of diet and exercise in growth restricted female rats on nephron endowment in male fetuses

Jessica F. Briffa; Sogand Gravina; Viktoria F. Richter; Dayana Mahizir; Kristina Anevska; Yeukai T. M. Mangwiro; James S. M. Cuffe; Fadi Charchar; Glenn D. Wadley; Deanne H. Hryciw; Karen M. Moritz; Mary E. Wlodek

doi:10.1113/EP092622

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Impact of diet and exercise in growth restricted female rats on nephron endowment in male fetuses

Journal article

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Impact of diet and exercise in growth restricted female rats on nephron endowment in male fetuses

Jessica F. Briffa, Sogand Gravina, Viktoria F. Richter, Dayana Mahizir, Kristina Anevska, Yeukai T. M. Mangwiro, James S. M. Cuffe, Fadi Charchar, Glenn D. Wadley, Deanne H. Hryciw, …

Experimental Physiology, Vol.111(3), pp.1365-1386

2026

DOI: https://doi.org/10.1113/EP092622

PMID: 41137704

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Abstract

exercise

growth restriction

high-fat diet

kidney

nephron endowment

second generation

Uteroplacental insufficiency impairs kidney development and programs male-onset cardiorenal disease, which can be transmitted to subsequent generations. Maternal lifestyle factors can independently influence fetal kidney development, highlighting that the lifestyle of growth-restricted females can have further influence on F2 kidney development. In this study, we examined the impact of maternal growth restriction with or without additional lifestyle factors on F2 male kidney development. Uteroplacental insufficiency (Restricted) or sham (Control) surgery was performed on embryonic day 18 in Wistar-Kyoto rats. F1 females were fed a Chow or High-fat diet from weaning (5 weeks of age). At 16 weeks, females were randomly allocated to an exercise group: no exercise (Sedentary); exercised prior to and during pregnancy (Exercise); or exercised only during pregnancy (PregEx). Females were mated at 20 weeks, with F2 male kidneys collected (embryonic day 20). Maternal growth restriction alone reduced nephron endowment by 29%, whereas additional lifestyle factors in Restricted dams reduced nephron endowment by similar to 43%. Interestingly, Exercise only in High-fat dams did not alter nephron endowment, which is likely to be attributable to significant kidney remodelling and/or enhanced resource availability. This study demonstrates that growth-restricted dams that experience multiple maternal lifestyle factors (i.e. High-fat diet and PregEx) impair the development of male F2 kidneys to a more severe extent than fetuses exposed to maternal growth restriction alone or a single maternal lifestyle factor in dams of normal birth weight (i.e. high-fat feeding or exercise alone). Importantly, positive lifestyle interventions (Exercise) in a high-fat environment compounded by adverse metabolic programming (Restriction) can be beneficial to fetal kidney development, which might prevent the transgenerational programming of cardiorenal disease.

Details

Title: Impact of diet and exercise in growth restricted female rats on nephron endowment in male fetuses
Authors: Jessica F. Briffa (Corresponding Author) - The University of Melbourne
Sogand Gravina - The University of Melbourne
Viktoria F. Richter - The University of Melbourne
Dayana Mahizir - The University of Melbourne
Kristina Anevska - La Trobe University
Yeukai T. M. Mangwiro - La Trobe University
James S. M. Cuffe - The University of Queensland
Fadi Charchar - Federation University
Glenn D. Wadley - Deakin University
Deanne H. Hryciw - The University of Melbourne
Karen M. Moritz - The University of Queensland
Mary E. Wlodek - The University of Melbourne
Publication details: Experimental Physiology, Vol.111(3), pp.1365-1386
Publisher: Wiley-Blackwell Publishing Ltd.
Date published: 2026
DOI: 10.1113/EP092622
ISSN: 1469-445X
PMID: 41137704
Copyright note: © 2025 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Data Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Grants: Intergenerational transmission of gender-specific metabolic disease for offspring born small: maternal, paternal and embryonic roles, 1045602, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Grant note: 2013 Diabetes Australia Research Trust Research Project (Mary E. Wlodek)
Organisation Unit: School of Health - Biomedicine
Language: English
Record Identifier: 991186522702621
Output Type: Journal article

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