Transgenerational metabolic outcomes associated with uteroplacental insufficiency

Tran, Melanie, Gallo, Linda A., Jefferies, Andrew J., Moritz, Karen M. and Wlodek, Mary E. (2013) Transgenerational metabolic outcomes associated with uteroplacental insufficiency. Journal of Endocrinology, 217 1: 105-118. doi:10.1530/JOE-12-0560

Author Tran, Melanie
Gallo, Linda A.
Jefferies, Andrew J.
Moritz, Karen M.
Wlodek, Mary E.
Title Transgenerational metabolic outcomes associated with uteroplacental insufficiency
Journal name Journal of Endocrinology   Check publisher's open access policy
ISSN 0022-0795
Publication date 2013-04
Sub-type Article (original research)
DOI 10.1530/JOE-12-0560
Open Access Status
Volume 217
Issue 1
Start page 105
End page 118
Total pages 14
Place of publication Bristol, United Kingdom
Publisher BioScientifica Ltd.
Collection year 2014
Language eng
Abstract 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-restrictedmothers, 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) controland 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 β-cell mass (-29%). By contrast, F2 restricted females had increasedβ-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.
Keyword Pancreas
Insulin secretion
Glucose metabolism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
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