Maternal hypoxia as a model for intrauterine growth retardation: effects on insulin-like growth factors and their binding proteins

Pediatr Res. 1994 Aug;36(2):152-8. doi: 10.1203/00006450-199408000-00004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Fetal Growth Retardation / etiology*
  • Fetal Growth Retardation / metabolism*
  • Fetus / metabolism
  • Hypoxia / complications*
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • Liver / metabolism
  • Maternal-Fetal Exchange*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatomedin / metabolism*
  • Somatomedins / metabolism*

Substances

  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • RNA, Messenger
  • Receptors, Somatomedin
  • Somatomedins