母源性应激、胎盘 11β-羟类固醇脱氢酶 2 与人类婴儿 HPA 轴发育：心理社会和生理途径。
Maternal stress, placental 11β-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways.
机构信息
Department of Anthropology, 301 Alumni Building CB #3115, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA; Carolina Population Center, 123 West Franklin Street, Chapel Hill, NC, 27516, USA.
Colegio de Ciencias de la Salud, Universidad San Francisco de Quito. Hospital de los Valles, Ed. Especialidades Médicas, PB, Av. Interoceánica Km. 12 ½; y Av. Florencia, Casilla Postal 17-1200-841, Quito, Ecuador; Galapagos Science Center. Avenida Alsacio Northia, Puerto Baquerizo Moreno, Ecuador San Cristobal, Galapagos Archipelago, Ecuador.
出版信息
Placenta. 2021 Jan 15;104:179-187. doi: 10.1016/j.placenta.2020.12.008. Epub 2020 Dec 24.
INTRODUCTION
Prenatal stress is known to influence fetal hypothalamic-pituitary-adrenal axis (HPA axis) development. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) is a central gene in this pathway, but little is known about what influences its functioning. We assess how maternal distress influences HSD11B2 functioning, and how HSD11B2 in turn, is associated with infant HPA axis development.
METHODS
Data come from 24 mother-infant dyads on the Galápagos Islands. Using adjusted linear regression models, we assess the effects of maternal psychosocial (stress and depressive symptoms, measured by the Perceived Stress Scale and the Patient Health Questionnaire-8, respectively) and physiological (HPA axis dysregulation) distress during pregnancy on HSD11B2 methylation and expression and then test how these HSD11B2 measures influence infant HPA axis development.
RESULTS
Maternal HPA axis dysregulation during pregnancy is associated with lower placental HSD11B2 expression, which is associated with an exaggerated cortisol reactivity in infants. Sex-specific analyses revealed that maternal depressive symptoms may influence the functioning of placental HSD11B2 differently in girls (n = 11, 46%) than in boys (n = 13, 54%), though the sample size was small.
DISCUSSION
These results support a disrupted adaptive framework, in which the ability to upregulate HSD11B2 expression in response to acute stress diminishes as maternal stress becomes chronic. In this model, chronic stress may exhaust the protective mechanism of HSD11B2, leaving the infant vulnerable to high levels of maternal cortisol, which could injure the fetal HPA axis and disrupt long-term neurobehavioral and metabolic development. While larger studies will be needed to confirm these findings, this study offers exploratory results on the effects of maternal distress on both HSD11B2 methylation and expression and the effect of HSD11B2 on offspring HPA axis development.
简介
产前压力已知会影响胎儿下丘脑-垂体-肾上腺轴（HPA 轴）的发育。胎盘 11β-羟类固醇脱氢酶 2（HSD11B2）是该途径中的一个核心基因，但人们对影响其功能的因素知之甚少。我们评估了母体应激如何影响 HSD11B2 的功能，以及 HSD11B2 反过来如何与婴儿 HPA 轴的发育相关。
方法
数据来自加拉帕戈斯群岛的 24 对母婴对。我们使用调整后的线性回归模型，评估了母亲的心理社会（压力和抑郁症状，分别通过感知压力量表和患者健康问卷-8 来衡量）和生理（HPA 轴失调）在怀孕期间的应激如何影响 HSD11B2 的甲基化和表达，然后测试这些 HSD11B2 测量值如何影响婴儿 HPA 轴的发育。
结果
孕妇 HPA 轴失调与胎盘 HSD11B2 表达降低有关，这与婴儿皮质醇反应过度有关。性别特异性分析表明，母亲的抑郁症状可能会以不同的方式影响女孩（n=11，46%）和男孩（n=13，54%）的胎盘 HSD11B2 功能，尽管样本量较小。
讨论
这些结果支持一个失调的适应性框架，在这个框架中，随着母体压力变得慢性，HSD11B2 表达上调的能力会减弱。在这个模型中，慢性应激可能会耗尽 HSD11B2 的保护机制，使婴儿易受母体皮质醇水平升高的影响，这可能会损害胎儿的 HPA 轴并破坏长期的神经行为和代谢发育。虽然需要更大的研究来证实这些发现，但本研究提供了关于母体应激对 HSD11B2 甲基化和表达的影响以及 HSD11B2 对后代 HPA 轴发育的影响的探索性结果。
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