Chronic prenatal hypoxia impairs cochlear development, a mechanism involving connexin26 expression and promoter methylation.
Chronic prenatal hypoxia impairs cochlear development, a mechanism involving connexin26 expression and promoter methylation.
复制标题
慢性产前缺氧损害耳蜗发育，其机制涉及连接蛋白26表达和启动子甲基化。
DOI：
10.3892/ijmm.2017.3303
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发表时间：
2018-03
影响因子：
5.4
通讯作者：
Zheng M
中科院分区：
文献类型：
--
作者：
Lin J;Huang H;Lv G;Xu X;Lin W;Xu X;Cheng J;Zheng M
慢性产前缺氧是对胎儿发育的一种损害，可能会产生各种后果，包括听力损失。间隙连接蛋白26(Cx26)是缝隙连接形成所需的主要蛋白质亚基之一，在维持耳蜗内环境平衡和正常听力方面起着重要作用。Cx26基因突变和表达异常与遗传性非综合征性耳聋密切相关，但Cx26基因突变和表达异常与产前缺氧的关系尚不明确。本研究旨在检测慢性产前低氧大鼠耳蜗区Cx26的表达和Cx26启动子区域的异常甲基化。苏木精-伊红染色显示缺氧组Corti器内毛细胞数量较少。逆转录-定量聚合酶链式反应和免疫印迹分析显示，缺氧组Cx26蛋白和mRNA水平均较对照组降低。进一步的亚硫酸氢盐测序分析显示，产前缺氧显著增加了Cx26基因启动子区域的甲基化状态。这些结果表明，慢性产前低氧导致听力损伤，并提示Cx26基因启动子区高甲基化和表达下调是其作用机制。
Chronic prenatal hypoxia is a damaging to fetal development and may have various consequences, including hearing loss. Connexin 26 (Cx26) is one of the major protein subunits required for gap junction formation, and has an important role in maintaining homeostasis in the cochlea and normal hearing. Cx26 mutation and expression abnormality are closely associated with inherited nonsyndromic deafness, but the association between Cx26 and prenatal hypoxia is less established. The present study aimed to examine Cx26 expression and aberrant methylation the Cx26 promoter region in the cochlea from rats exposed to chronic prenatal hypoxia. Hematoxylin and eosin staining demonstrated that the number of hair cells in the organ of Corti were less in the hypoxia group. Reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that protein and mRNA levels of Cx26 were decreased in the hypoxia group compared with the control group. Further bisulfite sequencing analysis revealed that prenatal hypoxia significantly increased the methylation status of the promoter region of the Cx26 gene. These results demonstrate that chronic prenatal hypoxia caused hearing impairment, and suggest that promoter region hypermethylation and expression downregulation of Cx26 underlie the mechanism of action.
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DOI：
10.1196/annals.1365.047
发表时间：
2006-01-01
期刊：
WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES
影响因子：
--
作者：
Eleftheriades, Makarios;Creatsas, George;Nicolaides, Kypros
通讯作者：
Nicolaides, Kypros
影响因子：
6.1
作者：
Chang, Qing;Tang, Wenxue;Lin, Xi
通讯作者：
Lin, Xi
影响因子：
2.8
作者：
Liu, Wei;Bostrom, Marja;Rask-Andersen, Helge
通讯作者：
Rask-Andersen, Helge
DOI：
10.1016/s0006-291x(03)01166-5
发表时间：
2003-07-25
影响因子：
3.1
作者：
Ahmad, S;Chen, SP;Lin, X
通讯作者：
Lin, X
DOI：
10.1016/j.bbrc.2005.08.037
发表时间：
2005-10-14
影响因子：
3.1
作者：
Shimizu, K;Hanaoka, M;Tsujiuchi, T
通讯作者：
Tsujiuchi, T