The role of the insulin-like growth factor system in prenatal growth.
Fetal growth is a complex process involving multiple environmental and genetic factors. Fetal growth restriction is associated with morbidity among small for gestational age (SGA) neonates as well as in children and adults who are former SGA infants. Over the last decade it has been recognized that the insulin-like growth factor axis has a critical role in mediating fetal and postnatal growth. However, how these hormones are involved in common pathological processes, leading to fetal growth restriction (FGR), remains unknown. In humans and mice, mutations or targeted deletions of the IGF ligands IGF1 and IGF2, as well as the IGF type-I receptor and its main signaling molecule IRS1 lead to FGR. IGFs are low in human SGA newborns; however, only a small minority of these infants have mutations of IGF-related molecules, rather, idiopathic or maternal factors are thought to induce FGR in most of these cases. Fetal growth is complex process governed by multiple genetic factors, but ultimately influenced by environmental processes, chief among them being nutrient supply from the mother to the placenta and from the placenta to the fetus. Understanding the molecular processes by which maternal factors contribute to fetal growth is an important step in developing strategies for diagnosing and treating different variants of fetal growth retardation. As our knowledge of these mechanisms become more sophisticated, we may find that many "idiopathic" cases of IUGR are also caused by subtle alterations in the IGF axis including heterozygotic mutations, polymorphisms, and epigenetic regulation.
Randhawa
Ruvdeep
R
Division of Endocrinology, Department of Pediatrics, Mattel Children's Hospital at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Cohen
Pinchas
P
D000818:Animals; D047109:Fetal Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II