Maternal nutrient restriction during early to mid gestation up-regulates cardiac insulin-like growth factor (IGF) receptors associated with enlarged ventricular size in fetal sheep

Growth Horm IGF Res. 2005 Aug;15(4):291-9. doi: 10.1016/j.ghir.2005.05.003.

Abstract

Intrauterine undernutrition is associated with a high incidence of cardiovascular diseases in adulthood. We previously showed that maternal nutrient restriction during early to mid gestation produces ventricular enlargement, although the mechanism is unknown. We examined myocardial expression of insulin-like growth factor I (IGF-1), IGF-2, IGF binding protein 3 (IGFBP-3), IGF-receptor 1 (IGF-1R) and IGF-2R in fetal sheep with maternal undernutrition. Multiparous ewes were fed with 50% (nutrient-restricted, NR) or 100% (control-fed, C) of NRC requirements from day 28 to 78 of gestation. Some of NR and C ewes were euthanized on day 78, and the rest were fed 100% NRC requirements from day 79 to 135 of gestation. At necropsy on day 78 or day 135 of gestation, gravid uteri were recovered. mRNA expression of IGF-1 and IGF-2 in ventricles were measured with RT-PCR, and protein expression of IGF-1R, IGF-2R, IGFBP-3 was quantitated with Western blot. Crown-rump length was reduced and left ventricle was enlarged in NR fetuses on day 78. At day 135 after re-alimentation, ventricular weights were similar between the two groups although ventricular wall thicknesses were greater in NR than C fetuses. No difference was found in IGF-1, IGF-2 or IGFBP-3 levels between the NR and C groups at either gestational age. Protein expression of IGF-1R and IGF-2R in the left ventricle and IGF-1R in the right ventricle was significantly elevated in the NR group on day 78 of gestation. Only IGF-1R expression remained elevated after late gestational re-alimentation in association with increases in ventricular wall thickness. Our study suggest that maternal undernutrition from early to mid gestation may change the expression of IGF-1R and IGF-2R in fetal myocardium, and play a role in cardiac ventricular enlargement in fetal sheep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animal Nutritional Physiological Phenomena*
  • Animals
  • Female
  • Fetus / chemistry
  • Gestational Age
  • Heart Ventricles / metabolism*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor II / genetics
  • Pregnancy
  • Pregnancy, Animal
  • RNA, Messenger / analysis
  • Receptor, IGF Type 1 / metabolism*
  • Receptor, IGF Type 2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep / metabolism*

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Messenger
  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1