title: The insulin-like growth factor system and fetal growth restrictionn.
abstract: Fetal growth is a complex process governed by multiple genetic factors, but ultimately influenced by environmental processes. 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-1 receptor (IGFR1) 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. Furthermore, the process of nutrient supply from the mother to the placenta and from the placenta to the fetus underlies the molecular mechanisms by which maternal factors contribute to fetal growth. Understanding these processes is an important step in developing strategies for diagnosing and treating different variants of FGR. 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.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Kaiser Permanente Southern California, Riverside Medical Center, Riverside, California 92505, USA. ruvdeep.s.randhawa@kp.org
authors.forename: Ruvdeep S
authors.initials: RS
authors.lastname: Randhawa
mesh_terms: D000818:Animals; D004777:Environment; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D005317:Fetal Growth Retardation / Q000209:etiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II