description): Fetal growth in utero is influenced by genetic, nutritional, hormonal and environmental factors. In the U.S., 8.6% of all live births are intrauterine growth restricted. Thirty percent of these growth restricted infants are at risk for adverse outcomes such as increased cardiovascular disease and glucose intolerance. Of the many factors that lead to intrauterine growth restriction, heme oxygenase-1 (HO-1) deficiency was recently associated with growth restriction in both humans and in mice. Fetal loss was also seen in both the human and mouse models. The HO-1 enzyme is rate limiting in bilirubin production. It serves to degrade heme and form carbon monoxide, a known vasodilator and neurotransmitter. Iron is also released and this metal can affect multiple genes via response elements. Through the metabolic reaction of HO-1, could expression of key growth factors and changes in vascular tone occur, leading to growth restriction? The investigators hypothesize that HO-1 deficiency causes increased fetal loss and growth restriction, and that HO-1 can influence growth by altering somatic and vascular growth factors such as IGF-1, leptin and VEGF.
The specific aims of this study are therefore to determine the rate and time of onset of fetal loss with HO-1 deficiency and to determine whether HO-1 deficiency in null mutant mice and with pharmacologic inhibition of HO activity, influences the expression of somatic growth factors such as IGF-1 in the placenta, uterus and fetal liver, and leptin in placenta and fetal serum. The investigators will also determine whether loss of HO-1 affects growth by modulating intra- or extra-embryonic HO-1 in chimeric animal tissue using tetraploid aggregation techniques.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD039248-02
Application #
6387775
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Spong, Catherine
Project Start
2000-07-12
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$79,476
Indirect Cost
Name
Stanford University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305