"健康和疾病的发育起源"(Developmental Origins of Health and Disease,DOHaD)学说认为,体内外环境可以通过影响胚胎/胎儿的遗传和表观遗传影响其发育轨迹,并对远期健康和疾病风险产生深远影响,其研究窗口目前已进一步扩展到配子发生期.配子发生和成熟需要数十年的时间,因此与胚胎和胎儿发育相比更容易受到较长暴露时间的潜在损害.糖尿病是威胁人类健康的重大慢性病,本文阐述了糖尿病的配子起源性,包括精子源性和卵子源性糖代谢异常的临床和基础研究进展,重点关注了表观遗传学机制在其中的作用,并展望了未来的研究方向.
Abstract
The"Developmental Origins of Health and Disease"theory(DOHaD)suggests that external environmental exposure on embryo and fetal can affect developmental trajectories leading to modification on long-term health and diseases risk through genetic and epigenetics inheritance,and its research window is now further extended to the stage of gametogenesis.It takes decades for gametes to develop and mature,so they are more vulnerable to potential damage from longer exposure times compared to embryonic and fetal development.Diabetes is one of the major chronic disease threatening human health.This article provides a comprehensive view of recent research progress on gamete-origins of diabetes,as well as animal models and related experimental research on sperm-and oocyte-origin glucose metabolism disorders.It also expounds the currently known phenotypes and mechanisms of gamete-origin glucose metabolism disorders,with a focus on the role of epigenetic mechanisms.Finally,future research directions are discussed.
维普
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