Sferruzzi-Perri Amanda N, Sandovici Ionel, Constancia Miguel, Fowden Abigail L
Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge, CB2 3EG, UK.
Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology and NIHR Cambridge Biomedical Research Centre, Robinson Way, Cambridge, CB2 0SW, UK.
J Physiol. 2017 Aug 1;595(15):5057-5093. doi: 10.1113/JP273330. Epub 2017 May 23.
The placenta is the main determinant of fetal growth and development in utero. It supplies all the nutrients and oxygen required for fetal growth and secretes hormones that facilitate maternal allocation of nutrients to the fetus. Furthermore, the placenta responds to nutritional and metabolic signals in the mother by altering its structural and functional phenotype, which can lead to changes in maternal resource allocation to the fetus. The molecular mechanisms by which the placenta senses and responds to environmental cues are poorly understood. This review discusses the role of the insulin-like growth factors (IGFs) in controlling placental resource allocation to fetal growth, particularly in response to adverse gestational environments. In particular, it assesses the impact of the IGFs and their signalling machinery on placental morphogenesis, substrate transport and hormone secretion, primarily in the laboratory species, although it draws on data from human and other species where relevant. It also considers the role of the IGFs as environmental signals in linking resource availability to fetal growth through changes in the morphological and functional phenotype of the placenta. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing adult-onset diseases in later life, understanding the role of IGFs during pregnancy in regulating placental resource allocation to fetal growth is important for identifying the mechanisms underlying the developmental programming of offspring phenotype by suboptimal intrauterine growth.
胎盘是子宫内胎儿生长发育的主要决定因素。它提供胎儿生长所需的所有营养物质和氧气,并分泌促进母体向胎儿分配营养的激素。此外,胎盘通过改变其结构和功能表型来响应母亲的营养和代谢信号,这可能导致母体对胎儿资源分配的变化。目前对胎盘感知和响应环境线索的分子机制了解甚少。本综述讨论了胰岛素样生长因子(IGFs)在控制胎盘向胎儿生长分配资源中的作用,特别是在应对不良妊娠环境时。特别是,它评估了IGFs及其信号传导机制对胎盘形态发生、底物转运和激素分泌的影响,主要是在实验物种中,尽管也借鉴了相关的人类和其他物种的数据。它还考虑了IGFs作为环境信号,通过胎盘形态和功能表型的变化将资源可用性与胎儿生长联系起来的作用。由于胎儿生长改变与围产期发病率和死亡率增加以及晚年患成人发病疾病的风险增加有关,了解孕期IGFs在调节胎盘向胎儿生长分配资源中的作用对于确定子宫内生长欠佳导致后代表型发育编程的潜在机制非常重要。