Jansson Thomas, Powell Theresa L
Department of Obstetrics and Gynecology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Clin Sci (Lond). 2007 Jul;113(1):1-13. doi: 10.1042/CS20060339.
Adverse influences during fetal life alter the structure and function of distinct cells, organ systems or homoeostatic pathways, thereby 'programming' the individual for an increased risk of developing cardiovascular disease and diabetes in adult life. Fetal programming can be caused by a number of different perturbations in the maternal compartment, such as altered maternal nutrition and reduced utero-placental blood flow; however, the underlying mechanisms remain to be fully established. Perturbations in the maternal environment must be transmitted across the placenta in order to affect the fetus. Here, we review recent insights into how the placenta responds to changes in the maternal environment and discuss possible mechanisms by which the placenta mediates fetal programming. In IUGR (intrauterine growth restriction) pregnancies, the increased placental vascular resistance subjects the fetal heart to increased work load, representing a possible direct link between altered placental structure and fetal programming of cardiovascular disease. A decreased activity of placental 11beta-HSD-2 (type 2 isoform of 11beta-hydroxysteroid dehydrogenase) activity can increase fetal exposure to maternal cortisol, which programmes the fetus for later hypertension and metabolic disease. The placenta appears to function as a nutrient sensor regulating nutrient transport according to the ability of the maternal supply line to deliver nutrients. By directly regulating fetal nutrient supply and fetal growth, the placenta plays a central role in fetal programming. Furthermore, perturbations in the maternal compartment may affect the methylation status of placental genes and increase placental oxidative/nitrative stress, resulting in changes in placental function. Intervention strategies targeting the placenta in order to prevent or alleviate altered fetal growth and/or fetal programming include altering placental growth and nutrient transport by maternally administered IGFs (insulin-like growth factors) and altering maternal levels of methyl donors.
胎儿期的不良影响会改变不同细胞、器官系统或体内平衡途径的结构和功能，从而使个体在成年后患心血管疾病和糖尿病的风险增加。胎儿编程可能由母体环境中的多种不同干扰因素引起，如母体营养改变和子宫 - 胎盘血流减少；然而，其潜在机制仍有待完全明确。母体环境中的干扰因素必须通过胎盘传递才能影响胎儿。在此，我们综述了关于胎盘如何响应母体环境变化的最新见解，并讨论了胎盘介导胎儿编程的可能机制。在宫内生长受限（IUGR）妊娠中，胎盘血管阻力增加使胎儿心脏工作负荷增加，这代表了胎盘结构改变与心血管疾病胎儿编程之间可能存在的直接联系。胎盘11β - HSD - 2（11β - 羟基类固醇脱氢酶2型同工酶）活性降低会增加胎儿对母体皮质醇的暴露，从而使胎儿日后易患高血压和代谢疾病。胎盘似乎起着营养传感器的作用，根据母体供应线输送营养物质的能力来调节营养物质的运输。通过直接调节胎儿营养供应和胎儿生长，胎盘在胎儿编程中发挥着核心作用。此外，母体环境中的干扰因素可能会影响胎盘基因的甲基化状态，并增加胎盘氧化/硝化应激，从而导致胎盘功能改变。旨在针对胎盘进行干预以预防或减轻胎儿生长改变和/或胎儿编程的策略包括通过母体给予胰岛素样生长因子（IGFs）来改变胎盘生长和营养物质运输，以及改变母体甲基供体的水平。
