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Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

ABSTRACT: We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Delta13) on maternal glucose concentrations in pregnancy.Experimental mice were pregnant females that had inherited the disrupted H19(Delta13) from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19(Delta13) through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19(Delta13), so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy.There were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19(Delta13)-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 +/- 378 vs. 1,386 +/- 107 mmol * min * l(-1) [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19(Delta13) mutants had significantly higher glucose concentrations during the last trimester (1,602 +/- 321 [n = 17] vs. 1,359 +/- 147 [n = 18] mmol * min * l(-1) [P = 0.009]).This study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19(Delta13). This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.

SUBMITTER: Petry CJ

PROVIDER: S-EPMC2797934 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

Petry Clive J CJ Evans Mark L ML Wingate Dianne L DL Ong Ken K KK Reik Wolf W Constância Miguel M Dunger David B DB

Diabetes 20090930 1

<h4>Objective</h4>We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19(Delta13) on maternal glucose concentrations in pregnancy.<h4>Research design and methods</h4>Experimental mice were pregnant females that had inherited the disrupted H19(Delta13) from their fathers and were therefore phenotypically wild type due to imprinting; app ...[more]

PMID: 19794064

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Project description:BACKGROUND:Higher birth weight is an important adverse outcome associated with hyperglycemia in pregnancy. Recent studies suggest that phthalate exposure is associated with elevated glucose levels in pregnant women, with implications for higher birth weight in the offspring. No study to date has investigated the association between prenatal phthalate exposure on infant high birth weight accounting for the range of pregnancy glucose levels. METHODS:A total of 350 women participating in an ongoing pregnancy cohort had data available on urinary phthalate metabolite concentrations at up to four time points across pregnancy. Urinary phthalate metabolites were averaged across pregnancy and log-transformed, specific gravity-adjusted and analyzed in quartiles. Birth weight was examined continuously (in grams), as well as dichotomized as large for gestational age (>90th percentile). Glucose levels were assessed based on Results from 50-g glucose challenge tests as a part of screening for gestational diabetes conducted at 24-28 weeks gestation, and grouped into 3 categories <120?mg/dL, 120-<140?mg/dL and ?140?mg/dL. Multivariable linear regression was performed, adjusting for potential confounders in the overall population and stratified by pregnancy glucose levels. RESULTS:Approximately 20% of infants born to women with glucose levels ?140?mg/dL were large for gestational age. Average mono-ethyl phthalate (MEP) concentrations were higher among women who had glucose levels ?140?mg/dL (geometric mean 140.9??g/L; 95% CI: 91.6-216.8); however, higher MEP concentrations were not associated with higher birth weight. When stratified by maternal glucose levels, there was a suggestive association between higher concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and higher birth weight among women with glucose levels ?140?mg/dL (adj. birth weight: 569.2?g; 95% CI: 14.1, 1178.2). CONCLUSIONS:Higher urinary phthalate metabolite concentrations were not significantly associated with higher birth weight. Counter to our hypothesis, women with higher glucose levels and higher urinary phthalate metabolites did not deliver babies with higher birth weight.

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Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

Publications

Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13.

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