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改善农场作物储存对母亲及其婴儿 DNA 甲基化的影响:来自肯尼亚的一项随机对照试验的证据。

Effects of improved on-farm crop storage on DNA methylation of mothers and their infants: evidence from a randomized controlled trial in Kenya.

机构信息

Institute of Psychology, Clinical Psychology and Psychotherapy, University of Zurich, Binzmuehlestrasse 14/Box 26, 8050, Zurich, Switzerland.

Aga Khan Hospital, Kisumu, Kenya.

出版信息

Clin Epigenetics. 2024 Jul 8;16(1):90. doi: 10.1186/s13148-024-01693-z.

Abstract

BACKGROUND

Stress during pregnancy can lead to adverse maternal and infant health outcomes through epigenetic changes in the hypothalamic-pituitary-adrenal axis. Among farmers in low-income countries, one important stressor is food insecurity, which can be reduced using hermetic storage bags. This study aimed to determine, for the first time, whether a hermetic storage bag intervention during pregnancy positively affects maternal and infant DNA methylation of the hypothalamic-pituitary-adrenal axis-related genes FKBP5 and NR3C1. We further analyzed whether anthropometrics, stress, and mental health were associated with DNA methylation.

METHODS

This study was part of a larger matched-pair randomized controlled trial focusing on the impact of improved on-farm storage on food security, poverty, and net income of smallholder farming households. A total of N = 149 mothers were recruited by telephone and invited to attend a study appointment at health facilities in Kakamega County, Western Kenya, with their infants in April or May 2021. During the appointment, anthropometric measurements were taken, questionnaires on stress and mental health were administered, and saliva samples were collected. Logistic and multiple linear regression were used to examine the effect of the intervention and related measures on DNA methylation.

RESULTS

Mothers in the intervention group showed higher mean NR3C1 methylation levels than those in the control group, corrected for multiple testing. Maternal postpartum body mass index was positively associated with infant NR3C1 CpG3 DNA methylation. The more stressful life events a mother had experienced in the previous 12 months (including during pregnancy), the lower her FKBP5 CpG3 methylation levels.

CONCLUSIONS

Food insecurity and stressful life events during pregnancy seem to exert significant effects on maternal DNA methylation. While these stressors did not appear to impact infant DNA methylation in the present study, maternal postpartum body mass index was significantly related to infant methylation. These findings suggest that while infants may be protected from excessive maternal glucocorticoids by placental barrier activity, maternal metabolic status is still reflected in their epigenetic make-up. Trial registration This study was part of a larger matched-pair randomized controlled trial on the impact of improved on-farm crop storage on welfare, nutrition, and human health. Registration can be found in the American Economic Association (AEA) RCT Registry, RCT ID: AEARCTR-0005845.

摘要

背景

孕期压力可通过下丘脑-垂体-肾上腺轴的表观遗传变化导致母婴健康不良结局。在低收入国家的农民中,一个重要的压力源是粮食不安全,使用密封储存袋可以减少这种情况。本研究首次旨在确定孕期使用密封储存袋干预是否会对与下丘脑-垂体-肾上腺轴相关的基因 FKBP5 和 NR3C1 的母婴 DNA 甲基化产生积极影响。我们还分析了人体测量学、压力和心理健康是否与 DNA 甲基化有关。

方法

本研究是一项更大的配对随机对照试验的一部分,重点研究了改善农场储存对小农家庭粮食安全、贫困和净收入的影响。共有 149 名母亲通过电话招募,并邀请她们于 2021 年 4 月或 5 月在肯尼亚西部卡卡梅加县的卫生设施参加研究预约,带着她们的婴儿。在预约期间,进行了人体测量,进行了关于压力和心理健康的问卷调查,并采集了唾液样本。逻辑回归和多元线性回归用于检验干预和相关措施对 DNA 甲基化的影响。

结果

经过多次检验校正后,干预组母亲的 NR3C1 甲基化水平均值高于对照组。母亲产后体重指数与婴儿 NR3C1 CpG3 DNA 甲基化呈正相关。母亲在过去 12 个月(包括孕期)经历的生活压力事件越多,其 FKBP5 CpG3 甲基化水平越低。

结论

孕期的粮食不安全和生活压力事件似乎对母亲的 DNA 甲基化有显著影响。虽然在本研究中,这些压力源似乎没有影响婴儿的 DNA 甲基化,但母亲产后体重指数与婴儿的甲基化明显相关。这些发现表明,尽管婴儿可能通过胎盘屏障活动免受母体糖皮质激素的过度影响,但母体的代谢状况仍反映在其表观遗传构成中。

试验注册

本研究是一项关于改善农场作物储存对福利、营养和人类健康影响的更大配对随机对照试验的一部分。注册信息可在美国经济协会(AEA) RCT 注册中心查询,RCT 编号:AEARCTR-0005845。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/11232227/4c899a000e1c/13148_2024_1693_Fig1_HTML.jpg

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