Localized fetomaternal hyperglycemia: spatial and kinetic definition by positron emission tomography.
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.


RESULTS
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
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.
Yao
Jianrong
J
Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
Wang
Chunlin
C
Walsh
Susan A
SA
Hu
Shanming
S
Sawatzke
Alexander B
AB
Dang
Diana
D
Segar
Jeffrey L
JL
Ponto
Laura L B
LL
Sunderland
John J
JJ
Norris
Andrew W
AW
D000818:Animals; D001158:Arteries / Q000000981:diagnostic imaging / Q000378:metabolism; D001692:Biological Transport; D002404:Catheterization; D005260:Female; D005333:Fetus; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006943:Hyperglycemia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D007700:Kinetics; D009035:Mothers; D049268:Positron-Emission Tomography; D011247:Pregnancy; D011248:Pregnancy Complications / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014599:Uterus / Q000098:blood supply; D051598:Whole Body Imaging
D019788:Fluorodeoxyglucose F18; D005947:Glucose