TY - JOUR
T1 - Maternal hypoxia as a model for intrauterine growth retardation
T2 - Effects on insulin-like growth factors and their binding proteins
AU - Tapanainen, Paivi J.
AU - Bang, Peter
AU - Wilson, Kristin
AU - Unterman, Terry G.
AU - Vreman, Hendrik J.
AU - Rosenfeld, Ron G.
PY - 1994/8
Y1 - 1994/8
N2 - 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 (1314% 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 1GF-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.
AB - 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 (1314% 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 1GF-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.
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U2 - 10.1203/00006450-199408000-00004
DO - 10.1203/00006450-199408000-00004
M3 - Article
C2 - 7526325
AN - SCOPUS:0028287587
SN - 0031-3998
VL - 36
SP - 152
EP - 158
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -