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孕期亚临床甲状腺功能减退对大鼠子代脑线粒体DNA甲基化的影响。

Effects of subclinical hypothyroidism during pregnancy on mtDNA methylation in the brain of rat offspring.

作者信息

Xie Liangzhuo, Huang Yangling, Ma Xiande, Ma Xiaoqiu, Wang Jian, Gao Tianshu, Chen Wei

机构信息

Liaoning University of Traditional Chinese Medicine, Shenyang City, Liaoning Province, P. R. China.

Experimental Animal Center of Liaoning, University of Traditional Chinese Medicine, Shenyang City, Liaoning Province, P. R. China.

出版信息

BMC Neurosci. 2025 Jan 24;26(1):6. doi: 10.1186/s12868-025-00930-2.

DOI:10.1186/s12868-025-00930-2
PMID:39856545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11762456/
Abstract

OBJECTIVE

This study aims to investigate the impact of subclinical hypothyroidism (SCH) during pregnancy on mitochondrial DNA (mtDNA) methylation in the brain tissues of rat offspring.

MATERIALS AND METHODS

Sixteen SD rats were randomly divided into two groups: control group (CON) and SCH group. BS-seq sequencing was used to analyze mtDNA methylation levels in the offspring's brain tissues; the 2,7-dichlorofluorescin diacetate (DCFH-DA) probe method was employed to detect reactive oxygen species (ROS) levels in brain tissues; electron microscopy was utilized to observe the mitochondrial structure in the hippocampal tissues of the offspring.

RESULTS

In the analysis of differentially methylated regions (DMRs), the mitochondrial chromosome in the SCH group exhibited 23 DMRs compared to the control group. ROS levels in the brain tissues of the SCH group were significantly higher than those in the control group (P < 0.05). The mitochondrial structure in the hippocampus of the SCH group was less intact compared to the CON group.

CONCLUSION

Subclinical hypothyroidism in pregnant rats may alter the mtDNA methylation pattern in the brains of their offspring, potentially affecting mitochondrial function and structure.

摘要

目的

本研究旨在探讨孕期亚临床甲状腺功能减退（SCH）对大鼠子代脑组织中线粒体DNA（mtDNA）甲基化的影响。

材料与方法

将16只SD大鼠随机分为两组：对照组（CON）和SCH组。采用亚硫酸氢盐测序法（BS-seq）分析子代脑组织中mtDNA甲基化水平；采用二氯二氢荧光素二乙酸酯（DCFH-DA）探针法检测脑组织中活性氧（ROS）水平；利用电子显微镜观察子代海马组织中的线粒体结构。

结果

在差异甲基化区域（DMR）分析中，与对照组相比，SCH组的线粒体染色体呈现出23个DMR。SCH组脑组织中的ROS水平显著高于对照组（P < 0.05）。与CON组相比，SCH组海马体中的线粒体结构完整性较差。

结论

孕鼠亚临床甲状腺功能减退可能会改变其子代大脑中的mtDNA甲基化模式，潜在地影响线粒体功能和结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/22708b9a65b7/12868_2025_930_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/c4bdb8a47568/12868_2025_930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/dc74bea5f4f4/12868_2025_930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/a7ce3c90acb0/12868_2025_930_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/8164bdff0e03/12868_2025_930_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/32cd6a0f4c91/12868_2025_930_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/22708b9a65b7/12868_2025_930_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/c4bdb8a47568/12868_2025_930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/dc74bea5f4f4/12868_2025_930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/a7ce3c90acb0/12868_2025_930_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/8164bdff0e03/12868_2025_930_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/32cd6a0f4c91/12868_2025_930_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbc/11762456/22708b9a65b7/12868_2025_930_Fig6_HTML.jpg

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Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats.母体甲状腺功能减退症导致大鼠母胎界面的氧化应激和内质网应激。
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Subclinical hypothyroidism in pregnancy rats impaired offspring's spatial learning and memory and the cerebellar development.
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Biochem Biophys Res Commun. 2022 Apr 30;602:63-69. doi: 10.1016/j.bbrc.2022.02.107. Epub 2022 Mar 1.
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Hypothyroidism induces oxidative stress and DNA damage in breast.甲状腺功能减退会在乳腺中引发氧化应激和DNA损伤。
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