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The insulin-like growth factor system and fetal growth restrictionn

Ruvdeep S Randhawa¹

¹Division of Pediatric Endocrinology, Department of Pediatrics, Kaiser Permanente Southern California, Riverside Medical Center, Riverside, California 92505, USA. ruvdeep.s.randhawa@kp.org

Pediatric Endocrinology Reviews : PER

|February 10, 2009

Insights

Fetal growth restriction (FGR) is linked to the insulin-like growth factor (IGF) axis. Understanding nutrient transport and IGF signaling is key to diagnosing and treating FGR, especially idiopathic cases.

Area of Science:

Reproductive Biology
Developmental Biology
Endocrinology

Background:

Fetal growth restriction (FGR) impacts neonates, children, and adults, with the insulin-like growth factor (IGF) axis recognized for its critical role in growth.
While genetic mutations in the IGF axis cause FGR, most cases are idiopathic or linked to maternal factors, with the underlying mechanisms poorly understood.

Purpose of the Study:

To explore the role of the insulin-like growth factor (IGF) axis in fetal growth restriction (FGR).
To investigate the molecular mechanisms of nutrient supply from mother to fetus and their contribution to FGR.
To identify potential diagnostic and therapeutic strategies for FGR.

Main Methods:

Review of genetic studies on IGF ligands (IGF1, IGF2), IGF type-1 receptor (IGFR1), and IRS1 in humans and mice.
Analysis of the role of maternal nutrient supply to the placenta and fetus in regulating fetal growth.
Exploration of subtle alterations in the IGF axis, including genetic variations and epigenetic regulation, in idiopathic FGR.

Main Results:

Mutations in IGF ligands, IGFR1, and IRS1 are associated with FGR in humans and mice.
Low IGF levels are observed in small for gestational age (SGA) newborns, but genetic mutations are rare.
Maternal factors influencing nutrient supply are critical in the pathogenesis of FGR.

Conclusions:

The IGF axis plays a crucial role in fetal growth, and its dysregulation contributes to FGR.
Understanding nutrient transport and IGF signaling pathways is essential for managing FGR.
Idiopathic FGR may involve subtle IGF axis alterations, including genetic polymorphisms and epigenetic modifications, offering avenues for future research and therapeutic development.

Read full analysis

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.

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