Molecular approach to intrauterine growth retardation: an overview of recent data.

Consideration of the abnormal regulation of fetal growth leading to intrauterine growth retardation must take account of the fundamental differences between the regulation of growth before and after birth. The significance of endocrine regulators of growth differs greatly in utero. During the first trimester of pregnancy, embryonic growth might be controlled at the level of the individual organs by nutrient supply and by locally active growth factors. Later, fetal growth depends essentially upon materno-placental cooperation in delivering nutrients to the fetus. Therefore the major role of hormones in fetal growth is to mediate utilization of available substrate. Fetal growth seems to be regulated by fetal insulin, IGF-1 and certainly IGF-2, while growth hormone has only a secondary role to play. In late gestation, placental size and fetal growth rate are well correlated, pointing to a key role of the placenta in the regulation of fetal growth. It is therefore of importance to understand the molecular mechanisms involved in regulating placental development and endocrine functions. TGF alpha and EGF might play a major role as suggested by the modulation of their receptors with placental development, and by the specific alterations of epidermal growth factor receptors in intrauterine growth retardation. In addition, human placenta secretes specifically placental growth hormone. The concentration of placental growth hormone is significantly decreased in sera of pregnant women bearing a fetus with intrauterine growth retardation.