Departments of Physiology, Obstetrics and Gynaecology and Medicine, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health Systems, Toronto, Ontario, Canada.
J Neuroendocrinol. 2019 Mar;31(3):e12674. doi: 10.1111/jne.12674. Epub 2019 Feb 1.
Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first-generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long-term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non-coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long-term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre-clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.
父母在怀孕前或怀孕期间暴露于压力或糖皮质激素会对后代的神经发育、神经内分泌功能和行为产生深远影响。具体结果取决于暴露的性质、强度和时间,以及受试动物的物种、性别和年龄。最近,人们已经明显认识到,其结果并不仅限于第一代后代,而且可能存在代际和跨代效应的传递。人们强烈关注这种早期暴露导致长期和潜在跨代结果的机制,并且有强有力的新证据表明,表观遗传过程(组蛋白修饰、DNA 甲基化和小非编码 RNA)参与其中。这一领域的新知识可能允许开发可以预防、改善或逆转与早期逆境暴露相关的长期负面影响的干预措施。这篇综述将重点关注最新的研究成果,弥合人类和临床前研究之间的差距,并强调该领域存在的一些局限性、挑战和差距。