Alcohol-induced intrauterine growth retardation (IUGR) has long been recognized, yet there remains no biochemical explanation as to the etiology of this abnormality. This proposal aimed at elucidating this mechanism by investigating the relationship of growth factors (GFs) and growth inhibitors (GIs) to normal fetal growth and alcohol-induced IUGR. A miniature swine (Sinclair S-1) is used as an experimental model for this study because of the known alcoholic inclination of these animals. Four serial pregnancies are planned for six alcoholic sows and six alcohol naive controls. Sera from pregnant mother, fetuses and neonates, amniotic fluids at term, and amniotic fluids of mother sows when they are to be sacrificed during the different weeks of the 4th pregnancy, will be evaluated for the levels of epidermal growth factor, transforming growth factors and insulin-like growth factors. Fetal tissues from diagnosed IUGR and normal fetuses will be used to study their ability to synthesize these GFs in vitro. Tissue GF/GI and their membrane cognate receptors will be determined by immunohistochemistry; and their expression in tissues evaluated by in situ hybridization. Both Western and Northern blotting techniques will be employed to characterize these biochemical determinants. This study will yield pertinent information for: (a) the identification of plausible biochemical determinants that may be causual factors for alcohol-induced IUGR, and autocrine/ paracrine factors related to fetal growth, (b) the fitness of the miniature swine as an experimental model for symmetrical IUGR study and (c) the identification of potential markers for IUGR detection. Therefore, this investigation of is fundamental, clinical and potential therapeutic importance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007733-04
Application #
2044097
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1989-01-01
Project End
1993-12-31
Budget Start
1992-01-01
Budget End
1993-12-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Das, K; Stout, L E; Hensleigh, H C et al. (1991) Direct positive effect of epidermal growth factor on the cytoplasmic maturation of mouse and human oocytes. Fertil Steril 55:1000-4
Ji, H J; Zhang, Q Q; Leung, B S (1990) Survey of oncogene and growth factor/receptor gene expression in cancer cells by intron-differential RNA/PCR. Biochem Biophys Res Commun 170:569-75