Maternal hypoxia as a model for intrauterine growth retardation: effects on insulin-like growth factors and their binding proteins.
Evidence suggests that IGF and their binding proteins play a role in fetal growth, but more knowledge concerning their regulation is essential. We examined the expression of IGF and their binding proteins in experimental intrauterine growth-retarded (IUGR) rat fetuses of hypoxic dams (13-14% oxygen, d 14-21 of gestation). The mean body weight of the fetuses (d 21 of gestation, n = 72) of the six hypoxic dams was 24% lower (p < 0.0001) than the mean weight of the fetuses of six control dams (n = 82). Wet liver weights demonstrated a 20% decrease (p < 0.0001) and placentas a 10% decrease (p < 0.01) compared with control fetuses. The mean serum concentrations of immunoreactive IGF-I in both groups were low but did not differ significantly. The mean serum concentrations of immunoreactive IGF-II, however, were higher in IUGR fetuses. As assessed by Northern blot analysis, there was a 4-fold increase in insulin-like growth factor binding protein-1 (IGFBP-1) mRNA expression in the livers of the IUGR fetuses compared with controls. IGFBP-2 mRNA expression was 6-fold increased in IUGR fetal livers. No difference was found in IGFBP-4 mRNA. An increase in IGFBP-1, -2, and -4 concentrations could be seen by Western ligand blotting in the serum of growth-retarded fetuses compared with control fetuses. This finding was verified by immunoprecipitation with specific antibodies, which demonstrated increases in IGFBP-1 and IGFBP-2. Our results validate the use of maternal hypoxia as an experimental model of intrauterine growth retardation and indicate that increased IGFBP-1 and -2 expression may be of importance in the etiology of fetal growth retardation caused by maternal hypoxia.
Tapanainen
P J
PJ
Department of Pediatrics, Stanford University, California 94305.
Bang
P
P
Wilson
K
K
Unterman
T G
TG
Vreman
H J
HJ
Rosenfeld
R G
RG
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D000860:Hypoxia / Q000150:complications*; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D013002:Somatomedins