Transgenerational metabolic outcomes associated with uteroplacental insufficiency

Melanie Tran; Linda A. Gallo; Andrew J. Jefferies; Karen M. Moritz; Mary E. Wlodek

doi:10.1530/JOE-12-0560

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Transgenerational metabolic outcomes associated with uteroplacental insufficiency

Journal article

Peer reviewed

Transgenerational metabolic outcomes associated with uteroplacental insufficiency

Melanie Tran, Linda A. Gallo, Andrew J. Jefferies, Karen M. Moritz and Mary E. Wlodek

Journal of Endocrinology, Vol.217(1), pp.105-118

2013

DOI: https://doi.org/10.1530/JOE-12-0560

PMID: 23420315

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Abstract

pancreas

insulin secretion

glucose metabolism

gender

ageing

Intrauterine growth restriction increases adult metabolic disease risk with evidence to suggest that suboptimal conditions in utero can have transgenerational effects. We determined whether impaired glucose tolerance, reduced insulin secretion, and pancreatic deficits are evident in second-generation (F2) male and female offspring from growth-restricted mothers, in a rat model of uteroplacental insufficiency. Late gestation uteroplacental insufficiency was induced by bilateral uterine vessel ligation (restricted) or sham surgery (control) in Wistar-Kyoto rats. First-generation (F1) control and restricted females were mated with normal males and F2 offspring studied at postnatal day 35 and at 6 and 12 months. F2 glucose tolerance, insulin secretion, and sensitivity were assessed at 6 and 12 months and pancreatic morphology was quantified at all study ages. At 6 months, F2 restricted male offspring exhibited blunted first-phase insulin response (-35%), which was associated with reduced pancreatic beta-cell mass (-29%). By contrast, F2 restricted females had increased b-cell mass despite reduced first-phase insulin response (-38%). This was not associated with any changes in plasma estradiol concentrations. Regardless of maternal birth weight, F2 control and restricted males had reduced homeostatic model assessment of insulin resistance and elevated plasma triglyceride concentrations at 6 months and reduced whole-body insulin sensitivity at 6 and 12 months compared with females. We report that low maternal birth weight is associated with reduced first-phase insulin response and gender-specific differences in pancreatic morphology in the F2. Further studies will define the mode(s) of disease transmission, including direct insults to developing gametes, adverse maternal responses to pregnancy, or inherited mechanisms.

Details

Title: Transgenerational metabolic outcomes associated with uteroplacental insufficiency
Authors: Melanie Tran (Author) - University of Melbourne
Linda A. Gallo (Author) - University of Melbourne
Andrew J. Jefferies (Author) - University of Melbourne
Karen M. Moritz (Author) - University of Queensland
Mary E. Wlodek (Corresponding Author) - University of Melbourne
Publication details: Journal of Endocrinology, Vol.217(1), pp.105-118
Publisher: Bioscientifica Ltd.
DOI: 10.1530/JOE-12-0560
ISSN: 1479-6805
PMID: 23420315
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99679193802621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Endocrinology & Metabolism

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