Randhawa Ruvdeep S
Division of Pediatric Endocrinology, Department of Pediatrics, Kaiser Permanente Southern California, Riverside Medical Center, Riverside, California 92505, USA.
Pediatr Endocrinol Rev. 2008 Dec;6(2):235-40.
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.
胎儿生长是一个由多种遗传因素控制的复杂过程，但最终会受到环境因素的影响。胎儿生长受限与小于胎龄（SGA）新生儿以及曾为SGA婴儿的儿童和成人的发病情况相关。在过去十年中，人们已经认识到胰岛素样生长因子轴在介导胎儿和出生后生长方面起着关键作用。然而，这些激素如何参与导致胎儿生长受限（FGR）的常见病理过程仍不清楚。在人类和小鼠中，IGF配体IGF1和IGF2、IGF 1型受体（IGFR1）及其主要信号分子IRS1的突变或靶向缺失会导致FGR。人类SGA新生儿的IGF水平较低；然而，这些婴儿中只有一小部分有IGF相关分子的突变，相反，在大多数情况下，特发性或母体因素被认为会诱发FGR。此外，从母亲到胎盘以及从胎盘到胎儿的营养供应过程是母体因素影响胎儿生长的分子机制基础。了解这些过程是制定诊断和治疗不同类型FGR策略的重要一步。随着我们对这些机制的认识变得更加深入，我们可能会发现许多“特发性”宫内生长受限病例也是由IGF轴的细微改变引起的，包括杂合突变、多态性和表观遗传调控。
