Lester Barry M, Conradt Elisabeth, LaGasse Linda L, Tronick Edward Z, Padbury James F, Marsit Carmen J
Center for the Study of Children at Risk, Providence, Rhode Island;
Warren Alpert Medical School, Brown University, Providence, Rhode Island.
Pediatrics. 2018 Oct;142(4). doi: 10.1542/peds.2017-1890.
: media-1vid110.1542/5804912859001PEDS-VA_2017-1890 OBJECTIVES: We sought to determine if variations in maternal care alter DNA methylation in term, healthy, 5-month-old infants. This work was based on landmark studies in animal models demonstrating that nurturing care by dams would alter their newborns' stress responses through epigenetic mechanisms. We used breastfeeding as a proxy for animal maternal behavior. We hypothesized alterations in DNA methylation of the glucocorticoid receptor gene and less hypothalamic stress response in infants of mothers who breastfed their infants versus infants of mothers who did not breastfeed.
A cohort study of term, healthy infants and their mothers who did ( = 21) or did not ( = 21) breastfeed for the first 5 months was used in this analysis. Cortisol stress reactivity was measured in infant saliva by using a mother-infant interaction procedure and DNA methylation of an important regulatory region of the glucocorticoid receptor gene. Changes in DNA methylation of this gene in humans were compared to homologous regions of the rat gene. DNA samples were prepared from cheek swabs and subjected to quantitative analysis of the extent of methylation by using sensitive sequencing techniques.
Breastfeeding was associated with decreased DNA methylation of the glucocorticoid receptor promoter and decreased cortisol reactivity in 5-month-old infants. Decreased DNA methylation occurred in the promoter region involved in regulation of the hypothalamic-pituitary-adrenal and immune system responses.
Maternal care in humans may impact the hypothalamic-pituitary-adrenal stress response through behavioral programming and manifest as offspring epigenetic change. These results explain, in part, some of the positive effects observed in children who are breastfed.
媒体-1视频110.1542/5804912859001《儿科学-VA》2017-1890 目的：我们试图确定母亲护理方式的差异是否会改变足月、健康的5个月大婴儿的DNA甲基化。这项工作基于动物模型的里程碑式研究，表明母鼠的悉心照料会通过表观遗传机制改变其新生幼崽的应激反应。我们将母乳喂养作为动物母性行为的替代指标。我们假设，与未母乳喂养婴儿的母亲所生婴儿相比，母乳喂养婴儿的母亲所生婴儿的糖皮质激素受体基因DNA甲基化会发生改变，且下丘脑应激反应会减弱。
本分析采用了一项队列研究，研究对象为足月、健康的婴儿及其母亲，其中21名母亲进行了5个月的母乳喂养，21名母亲未进行母乳喂养。通过母婴互动程序测量婴儿唾液中的皮质醇应激反应性，并检测糖皮质激素受体基因一个重要调控区域的DNA甲基化情况。将该基因在人类中的DNA甲基化变化与大鼠基因的同源区域进行比较。从颊拭子中制备DNA样本，并使用灵敏的测序技术对甲基化程度进行定量分析。
母乳喂养与5个月大婴儿糖皮质激素受体启动子的DNA甲基化降低以及皮质醇反应性降低有关。DNA甲基化降低发生在参与下丘脑-垂体-肾上腺和免疫系统反应调节的启动子区域。
人类的母亲护理可能通过行为编程影响下丘脑-垂体-肾上腺应激反应，并表现为后代的表观遗传变化。这些结果部分解释了母乳喂养儿童所观察到的一些积极影响。
