Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
The Farncombe Family Digestive Diseases Research Institute, McMaster University, Hamilton, Canada.
J Endocrinol. 2019 Jul 1;242(1):T51-T68. doi: 10.1530/JOE-19-0048.
It is well established that early life environmental signals, including nutrition, set the stage for long-term health and disease risk - effects that span multiple generations. This relationship begins early, in the periconceptional period and extends into embryonic, fetal and early infant phases of life. Now known as the Developmental Origins of Health and Disease (DOHaD), this concept describes the adaptations that a developing organism makes in response to early life cues, resulting in adjustments in homeostatic systems that may prove maladaptive in postnatal life, leading to an increased risk of chronic disease and/or the inheritance of risk factors across generations. Reproductive maturation and function is similarly influenced by early life events. This should not be surprising, since primordial germ cells are established early in life and thus vulnerable to early life adversity. A multitude of 'modifying' cues inducing developmental adaptations have been identified that result in changes in reproductive development and impairments in reproductive function. Many types of nutritional challenges including caloric restriction, macronutrient excess and micronutrient insufficiencies have been shown to induce early life adaptations that produce long-term reproductive dysfunction. Many pathways have been suggested to underpin these associations, including epigenetic reprogramming of germ cells. While the mechanisms still remain to be fully investigated, it is clear that a lifecourse approach to understanding lifetime reproductive function is necessary. Furthermore, investigations of the impacts of early life adversity must be extended to include the paternal environment, especially in epidemiological and clinical studies of offspring reproductive function.
众所周知，早期生活环境信号（包括营养）为长期健康和疾病风险奠定了基础——这种影响跨越了多个世代。这种关系始于受孕前阶段，并延伸至胚胎、胎儿和婴儿早期生命阶段。现在被称为健康与疾病的发育起源（DOHaD），这个概念描述了一个发育中的生物体对早期生命线索做出的适应，导致体内平衡系统的调整，这些调整在出生后可能是适应不良的，并导致慢性疾病风险增加和/或风险因素在代际间遗传。生殖成熟和功能同样受到早期生活事件的影响。这并不奇怪，因为原始生殖细胞早在生命早期就已经建立，因此容易受到早期生活逆境的影响。已经确定了许多“修饰”线索，这些线索诱导了发育适应，导致生殖发育的变化和生殖功能的障碍。许多类型的营养挑战，包括热量限制、大量营养素过剩和微量营养素不足，已被证明会诱导早期生活适应，从而导致长期生殖功能障碍。许多途径被认为是这些关联的基础，包括生殖细胞的表观遗传重编程。虽然这些机制仍有待充分研究，但很明显，需要采用终生方法来理解终生生殖功能。此外，必须将早期生活逆境的影响调查扩展到包括父方环境，特别是在后代生殖功能的流行病学和临床研究中。
