Watkins A J, Lucas E S, Fleming T P
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
J Dev Orig Health Dis. 2010 Apr;1(2):87-95. doi: 10.1017/S2040174409990195.
The periconceptional period of mammalian development has been identified as an early 'developmental window' during which environmental conditions may influence the pattern of future growth and physiology. Studies in humans and animal models have revealed that factors such as maternal nutritional status or in vitro culture and manipulation of developing gametes and preimplantation embryos can impact upon the long-term health and physiology of the offspring. However, the mechanisms involved in the programming of adult disease in response to altered periconceptional development require increased investigation. The role of epigenetic modifications to DNA and chromatin organisation has been identified as a likely mechanism through which environmental perturbations can affect gene expression patterns resulting in phenotypic change. This study will highlight the sensitivity of two critical stages in early mammalian development, gametogenesis and preimplantation development. We will detail how changes to the immediate environment can not only impact upon developmental processes taking place at that time, but can also affect long-term aspects of offspring health and physiology. We will also discuss the emerging role of epigenetics as a mechanistic link between the environment and the later phenotype of the developing organism.
哺乳动物发育的围孕期已被确定为一个早期的“发育窗口”,在此期间,环境条件可能会影响未来的生长模式和生理机能。对人类和动物模型的研究表明,诸如母体营养状况或发育中的配子及植入前胚胎的体外培养与操作等因素,会影响后代的长期健康和生理机能。然而,针对围孕期发育改变所引发的成人疾病编程机制,仍需进一步深入研究。DNA和染色质组织的表观遗传修饰作用,已被确认为一种可能的机制,通过该机制,环境扰动能够影响基因表达模式,进而导致表型变化。本研究将着重强调哺乳动物早期发育中两个关键阶段——配子发生和植入前发育——的敏感性。我们将详细阐述即时环境的变化不仅如何影响当时正在发生的发育过程,还如何影响后代健康和生理机能的长期状况。我们还将讨论表观遗传学作为环境与发育中生物体后期表型之间的一种机制性联系所发挥的新作用。