Fowden A L, Valenzuela O A, Vaughan O R, Jellyman J K, Forhead A J
Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Domest Anim Endocrinol. 2016 Jul;56 Suppl:S121-32. doi: 10.1016/j.domaniend.2016.02.014.
Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring.
糖皮质激素（GCs）是子宫内发育过程中重要的环境和成熟信号。临近足月时，胎儿糖皮质激素受体浓度的成熟性升高会减缓胎儿生长，并诱导新生儿生存所必需的关键组织分化。当由于胎儿生长的条件欠佳导致孕期早期皮质醇水平升高时，从组织增生到分化的转变会过早开始，这会改变由受孕时遗传的基因型所发育出的表型。尽管这会提高分娩时存活的几率，但对出生后的后代也会产生长期的功能影响。因此，糖皮质激素也是编程信号，在子宫内发育期间永久性地改变组织结构和功能，以优化后代的适应性。然而，如果出生后的环境条件与子宫内所发出的信号不同，早期糖皮质激素受体过度暴露的表型结果可能会变得适应不良，并导致成年后出现生理功能障碍。本综述主要聚焦于农场动物物种，重点探讨糖皮质激素在发育编程中的作用。它研究了影响子宫内糖皮质激素生物利用度的因素，以及糖皮质激素对足月时和孕期早期胎儿组织和器官系统发育的影响。它还讨论了生命早期糖皮质激素过度暴露的易感性窗口，以及糖皮质激素编程的分子机制和长期后果，特别强调了后代的心血管、代谢和内分泌表型。
