Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Environ Res Public Health. 2021 Sep 6;18(17):9380. doi: 10.3390/ijerph18179380.
Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the 'Developmental Origins of Health and Disease' (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.
受孕前后的环境会影响发育过程，对妊娠和产后表型产生持久影响，并对成年后的健康和疾病风险产生影响。受孕前后的环境暴露是“健康与疾病的发育起源”（DOHaD）概念的重要组成部分。在这篇综述中，我们考虑了在特定人类模型和蛋白质限制的小鼠实验模型中，受孕前后母体营养不良的影响。人类数据集表明，受孕前后的宏量营养素缺乏会影响表观基因组，对心血管代谢和神经健康产生持久影响。仅在受孕前后的母体低蛋白饮食的小鼠模型揭示了在诱导母体代谢物缺乏后，发育编程的逐步改变。这一进展包括对胚胎外和胚胎细胞谱系和组织的不同影响，导致生长轨迹的失调和慢性疾病合并症的增加。该时间线涵盖了一系列营养感应和信号、细胞、代谢、表观遗传和生理过程的机制，其中 mTORC1 信号被提议起到协调作用。早期胚胎似乎积极参与环境感应，以优化发育过程以实现生存，但代价是以后会出现疾病。其他受孕前后的环境体验，包括母体营养过剩、微量营养素的可获得性、污染物暴露以及辅助生殖治疗（ART），可能会导致类似的不良健康后果，并支持在怀孕前进行孕前健康。
