IGFs and Feto-placental Growth

Abigail Fowden
Department of Physiology; University of Cambridge

The insulin like growth factors, IGF-I and IGF-II, have a key role in regulating fetal growth throughout gestation. They have metabolic, mitogenic and differentiative activities in a wide range of fetal tissues including the placenta. They act as progression factors in the cell cycle and increase DNA synthesis and cell differentiation in several different fetal cell types in vitro (1). In contrast to the adult, the Igf2 gene is expressed widely in the fetus (1). Tissue abundance of IGF-II mRNA is high in utero compared to postnatal values although down-regulation of expression does occur in certain fetal tissues immediately before birth (2). In the placenta and several other fetal tissues, the IGF-II gene is imprinted and expressed only from the paternal allele. However, imprinting of the Igf2 gene is tissue specific and is not seen for instance in the fetal brain in sheep and cows. Tissues, such as the liver, also show a developmental switch from Igf2 imprinting in utero to biallelic expression postnatally in species such as sheep, cows and humans although not in the mouse. In part, the effects of IGF-II on fetal growth are likely to be mediated through changes in the size and functional capacity of the placenta. In mice, placental growth is stimulated by IGF-II via both its paracrine and endocrine actions (3). Our most recent studies have also suggested that nutrient transfer across the murine placenta is affected by specific placental Igf2 gene transcripts (4). In contrast to IGF-II, gene expression and circulating levels of IGF-I are low in utero but rise rapidly after birth. Conditions which lead to fetal growth retardation, such as fasting hypoxia and placental insufficiency also have more pronounced effects on tissue and circulating levels of IGF-I than IGF-1I. In addition, birth bodyweight is more closed correlated with the concentration of plasma IGF-I than IGF-II (1). Fetal IGF-I may therefore have a more prominent role that fetal IGF-II is modulating cell proliferation in relation to the specific endocrine and nutritional conditions prevailing in utero. Fetal IGF-II, on the other hand, appears to provide the constitutive drive for growth in utero via effects on both fetal and placental tissues and may also be responsible for the developmental and tissue-specific changes in cell differentiation observed in these tissues towards term.


  1. Fowden, A.L. Reprod. Fert. Develop. 7: 351-363, 1995.

  2. Fowden , A.L. Proc. Soc. Nutr. 57: 113-122, 1998.

  3. Efstratiadis, A. Int. J. Dev. Biol. 42: 955-976, 1998.

  4. Constancia et al. This Meeting, 2002.