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Localized fetomaternal hyperglycemia: spatial and kinetic definition by positron emission tomography. PLoS One 2010 Aug 06;5(8):e12027

Date

08/12/2010

Pubmed ID

20700464

Pubmed Central ID

PMC2917372

DOI

10.1371/journal.pone.0012027

Scopus ID

2-s2.0-77957761086   9 Citations

Abstract

BACKGROUND: Complex but common maternal diseases such as diabetes and obesity contribute to adverse fetal outcomes. Understanding of the mechanisms involved is hampered by difficulty in isolating individual elements of complex maternal states in vivo. We approached this problem in the context of maternal diabetes and sought an approach to expose the developing fetus in vivo to isolated hyperglycemia in the pregnant rat.

METHODOLOGY AND PRINCIPAL FINDINGS: We hypothesized that glucose infused into the arterial supply of one uterine horn would more highly expose fetuses in the ipsilateral versus contralateral uterine horn. To test this, the glucose tracer [18F]fluorodeoxyglucose (FDG) was infused via the left uterine artery. Regional glucose uptake into maternal tissues and fetuses was quantified using positron emission tomography (PET). Upon infusion, FDG accumulation began in the left-sided placentae, subsequently spreading to the fetuses. Over two hours after completion of the infusion, FDG accumulation was significantly greater in left compared to right uterine horn fetuses, favoring the left by 1.9+/-0.1 and 2.8+/-0.3 fold under fasted and hyperinsulinemic conditions (p<10(-11) n=32-35 and p<10(-12) n=27-45) respectively. By contrast, centrally administered [3H]-2-deoxyglucose accumulated equally between the fetuses of the two uterine horns. Induction of significant hyperglycemia (10(3) mg/dL) localized to the left uterine artery was sustained for at least 48 hours while maternal euglycemia was maintained.

CONCLUSIONS AND SIGNIFICANCE: This approach exposes selected fetuses to localized hyperglycemia in vivo, minimizing exposure of the mother and thus secondary effects. Additionally, a set of less exposed internal control fetuses are maintained for comparison, allowing direct study of the in vivo fetal effects of isolated hyperglycemia. Broadly, this approach can be extended to study a variety of maternal-sided perturbations suspected to directly affect fetal health.

Author List

Yao J, Wang C, Walsh SA, Hu S, Sawatzke AB, Dang D, Segar JL, Ponto LL, Sunderland JJ, Norris AW

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arteries
Biological Transport
Catheterization
Female
Fetus
Fluorodeoxyglucose F18
Glucose
Hyperglycemia
Kinetics
Mothers
Positron-Emission Tomography
Pregnancy
Pregnancy Complications
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Uterus
Whole Body Imaging
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00