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患有胎盘植入谱系疾病的女性胎盘内DNA甲基转移酶水平升高,导致DNA甲基化模式异常。

Increased levels of DNA methyltransferases in the placentas of women affected by Placenta Accreta Spectrum lead to aberrant DNA methylation patterns.

作者信息

Uysal Fatma, Bozdemir Nazlıcan, Kisar Selin, Sukur Gozde, Sayal Hasan Berkan, Korgun Emin Turkay

机构信息

Department of Histology and Embryology, Ankara Medipol University School of Medicine, Ankara, Turkey.

Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.

出版信息

J Mol Histol. 2024 Dec 4;56(1):28. doi: 10.1007/s10735-024-10302-5.

DOI:10.1007/s10735-024-10302-5
PMID:39630325
Abstract

Placenta Accreta Spectrum (PAS) is a serious placental abnormality assosiated with significant maternal death during pregnancy. Due to its invasive characteristics resembling tumor growth, PAS is often associated with tumor-related proteins. While DNA methylation is known to regulate genes involved in development, its potential role in the development of PAS remains unclear. The aim of our study was to investigate the impact of PAS on DNA methylation and DNA methyltransferases (DNMTs). The groups were categorized into three groups: vaginal birth, cesarean delivery, and cesarean delivery with PAS. To measure DNMT protein levels in placental tissue, we employed immunohistochemistry (IHC) and Western blot (WB) techniques. Global DNA methylation levels were assessed using 5-methylcytosine staining. We found that DNMT1, DNMT3A and DNMT3L levels were significantly increased in the placentas of PAS group compared to control counterparts in both WB and IHC analysis. Compatible with DNMTs expressions, global DNA methylation levels were found to be significantly higher in placentas from women with PAS compared to controls. Our results suggest that significant alterations in DNMTs expressions and global DNA methylation within placentas may contribute to the development of Placenta Accreta Spectrum (PAS). To elucidate the precise molecular mechanisms underlying these changes and their role in PAS pathogenesis, further research required.

摘要

胎盘植入谱系(PAS)是一种严重的胎盘异常,与孕期产妇的高死亡率相关。由于其侵袭性特征类似于肿瘤生长,PAS常与肿瘤相关蛋白有关。虽然已知DNA甲基化可调节参与发育的基因,但其在PAS发生发展中的潜在作用仍不清楚。我们研究的目的是调查PAS对DNA甲基化和DNA甲基转移酶(DNMTs)的影响。研究对象分为三组:经阴道分娩、剖宫产以及合并PAS的剖宫产。为了测量胎盘组织中DNMT蛋白水平,我们采用了免疫组织化学(IHC)和蛋白质印迹法(WB)技术。使用5-甲基胞嘧啶染色评估总体DNA甲基化水平。我们发现,在WB和IHC分析中,与对照组相比,PAS组胎盘组织中DNMT1、DNMT3A和DNMT3L的水平显著升高。与DNMTs的表达情况一致,与对照组相比,PAS患者胎盘组织中的总体DNA甲基化水平显著更高。我们的研究结果表明,胎盘组织中DNMTs表达和总体DNA甲基化的显著改变可能与胎盘植入谱系(PAS)的发生有关。为了阐明这些变化背后的确切分子机制及其在PAS发病机制中的作用,还需要进一步研究。

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