FETAL ADAPTATION TO CHRONIC UTERINE BLOOD FLOW REDUCTION

Project: Research project

Description

Intrauterine growth retardation is a significant cause of perinatal
morbidity and mortality. Maternal conditions which results in reduced
uteroplacental blood flow are consistently associated with fetal growth
retardation. The fetal metabolic adaptations which occur under these
conditions ensure survival of the fetus at he expense of growth. The
purpose of the present investigation is to elucidate the mechanisms
responsible for the adaptations which impact on fetal growth. The
proposed studies will examine the following hypotheses: 1) fetal hypoxia
due to uteroplacental blood flow reduction will decrease tissue insulin
like growth factor I (IGF-I) bioactivity which in turn will effect a
decrease in protein synthesis and accretion in selected tissues (skeletal
muscle), resulting in deceleration in growth rate. 2) the changes in IGF-
I bioactivity and protein metabolism can be reserved, at least in part,
through maternal (and thereby fetal) oxygen supplementation. 3) infusion
of IGF-I into the fetal hindlimb will result in increased protein
synthesis in skeletal muscle tissue. These hypotheses will be tested
using a model of prolonged uteroplacental blood flow reduction in the
sheep developed by the candidate. Daily measurements of linear fetal
growth will be made before and during 14 days of uteroplacental blood
flow reduction during which time the rates of protein synthesis,
breakdown, oxidation and net accretion in the whole fetal body as well
as in fetal skeletal muscle will be determined using stable and
radioactive tracer methodology. Skeletal muscle metabolism will be
examined using an in vivo fetal hindlimb. These studies will provide a broader understanding of the metabolic
processes which contribute to the development of fetal growth
retardation, thereby possibly stimulating new approaches to the
prevention and treatment of this condition in human pregnancies.
StatusFinished
Effective start/end date12/1/9311/30/98

Funding

  • National Institutes of Health: $80,006.00
  • National Institutes of Health: $85,045.00
  • National Institutes of Health
  • National Institutes of Health: $85,045.00
  • National Institutes of Health

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Skeletal Muscle
Fetal Growth Retardation
Hindlimb
Fetal Development
Insulin-Like Growth Factor I
Mothers
Proteins
Intercellular Signaling Peptides and Proteins
Deceleration
Growth
Fetus
Fetal Hypoxia
Radioactive Tracers
Oxygen
Pregnancy
Muscles
Perinatal Mortality
Sheep
Morbidity
Survival

ASJC

  • Medicine(all)