Meakin C J, Martin E M, Santos H P, Mokrova I, Kuban K, O'Shea T M, Joseph R M, Smeester L, Fry R C
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, USA.
Horm Behav. 2018 May;101:29-35. doi: 10.1016/j.yhbeh.2018.02.007. Epub 2018 Mar 5.
A major component of the neuroendocrine system is the hypothalamus-pituitary adrenal (HPA) axis. HPA axis genes are also known to play a role in placental physiology. Thus, disruptions in the signaling of HPA axis-associated genes may adversely impact the placenta as well as fetal development, with adverse consequences for health and development of the child. In support of this, recent studies have shown that placental epigenetic methylation of HPA axis genes has an impact on infant behavior. In this study, we evaluated CpG methylation of 14 placental HPA axis-associated genes from a subcohort (n=228) of the Extremely Low Gestational Age Newborns (ELGAN) cohort in relation to cognitive function in mid-childhood (e.g. 10 yrs). Multivariable logistic regression revealed that placental CpG methylation of 10 HPA-axis associated genes were significantly associated with cognition at age 10. Specifically, placental CpG methylation levels of the glucocorticoid receptor gene, Nuclear Receptor Subfamily Group 3 C Member 1 () and Brain-derived Neurotropic Factor () were significantly associated with increased odds in developing moderate/severe adverse cognitive impairment at age 10. Methyl-CpG Binding Protein 2 (MECP2) was the major transcriptional regulator of the ten identified HPA genes. The data suggest that placental CpG methylation is associated with cognitive outcomes in mid-childhood.
神经内分泌系统的一个主要组成部分是下丘脑-垂体-肾上腺（HPA）轴。已知HPA轴基因在胎盘生理学中也发挥作用。因此，HPA轴相关基因信号传导的破坏可能会对胎盘以及胎儿发育产生不利影响，进而对儿童的健康和发育造成不良后果。支持这一观点的是，最近的研究表明，HPA轴基因的胎盘表观遗传甲基化会影响婴儿行为。在本研究中，我们评估了极低孕周新生儿（ELGAN）队列中一个亚组（n = 228）的14个胎盘HPA轴相关基因的CpG甲基化与儿童中期（如10岁）认知功能的关系。多变量逻辑回归显示，10个HPA轴相关基因的胎盘CpG甲基化与10岁时的认知显著相关。具体而言，糖皮质激素受体基因、核受体亚家族3 C成员1（）和脑源性神经营养因子（）的胎盘CpG甲基化水平与10岁时发生中度/重度不良认知障碍的几率增加显著相关。甲基化CpG结合蛋白2（MECP2）是所确定的10个HPA基因的主要转录调节因子。数据表明，胎盘CpG甲基化与儿童中期的认知结果相关。
