Bordoni Laura, Petracci Irene, Calleja-Agius Jean, Lalor Joan G, Gabbianelli Rosita
Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, 62032 Camerino, Italy.
School of Advanced Studies, University of Camerino, 62032 Camerino, Italy.
Biomedicines. 2020 Dec 8;8(12):584. doi: 10.3390/biomedicines8120584.
Perinatal life represents a delicate phase of development where stimuli of all sorts, coming to or from the mother, can influence the programming of the future baby's health. These stimuli may have consequences that persist throughout adulthood. Nuclear receptor related 1 protein (NURR1), a transcription factor with a critical role in the development of the dopaminergic neurons in the midbrain, mediates the response to stressful environmental stimuli in the perinatal period. During pregnancy, low-grade inflammation triggered by maternal obesity, hyperinsulinemia or vaginal infections alters NURR1 expression in human gestational tissues. A similar scenario is triggered by exposure to neurotoxic compounds, which are associated with epigenetic deregulation in the offspring, with potential intergenerational effects. Since these alterations have been associated with an increased risk of developing late-onset diseases in children, NURR1, alone, or in combination with other molecular markers, has been proposed as a new prognostic tool and a potential therapeutic target for several pathological conditions. This narrative review describes perinatal stress associated with gene deregulation, which is proposed here as a mediator of late-onset consequences of early life events.
围产期是一个脆弱的发育阶段，来自母亲或作用于母亲的各种刺激都可能影响未来婴儿的健康编程。这些刺激可能会产生持续至成年期的后果。核受体相关1蛋白（NURR1）是一种在中脑多巴胺能神经元发育中起关键作用的转录因子，介导围产期对压力性环境刺激的反应。在怀孕期间，由母亲肥胖、高胰岛素血症或阴道感染引发的低度炎症会改变人类妊娠组织中NURR1的表达。接触神经毒性化合物也会引发类似情况，这与后代的表观遗传失调有关，并可能产生代际影响。由于这些改变与儿童患迟发性疾病的风险增加有关，因此NURR1单独或与其他分子标记物联合使用，已被提议作为一种新的预后工具和几种病理状况的潜在治疗靶点。这篇叙述性综述描述了与基因失调相关的围产期应激，本文将其提议为早期生活事件迟发后果的介导因素。
