Methylation alterations of imprinted genes in different placental diseases

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-09-18 DOI:10.1186/s13148-024-01738-3

Xuwei Wang, Yunyun Liu, Yuying Wu, Chunxi Lin, Si Yang, Yuhan Yang, Dunjin Chen, Bolan Yu

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Abstract

Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2′-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

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不同胎盘疾病中印记基因的甲基化改变

印迹基因在胎盘和妊娠过程中发挥着重要的功能，但有关它们在不同胎盘疾病中作用的研究却很有限。有研究认为，胎盘印记基因的表观遗传学改变（如DNA甲基化）可能导致严重胎盘疾病（如子痫前期（PE）和胎盘早剥谱系障碍（PAS））的不同病理特征。在这项研究中，我们分别采用亚硫酸氢盐测序聚合酶链反应（PCR）和定量 PCR 对 PE 和 PAS 胎盘印迹基因的甲基化和表达进行了比较分析。此外，我们还通过测定脐带血中8-羟基-2′-脱氧鸟苷水平来评估胎盘DNA的氧化损伤，并通过酶联免疫吸附测定法测定脐带血中胰岛素样生长因子2（IGF2）和皮质醇水平来评估胎儿的生长情况。结果表明，在 PE 胎盘和 PAS 胎盘中，钾电压门通道 Q 亚家族成员 1、GNAS 复合基因座、中胚层特异性转录本和 IGF2 的甲基化和表达均发生了显著变化。此外，我们的研究结果表明，与正常妊娠相比，母体印记基因在 PE 胎盘中明显表达过高，而在 PAS 胎盘中则明显表达过低。此外，在 PE 胎盘和 PAS 胎盘中，DNA 氧化损伤均升高，且与 IGF2 DNA 甲基化呈正相关，皮质醇和 IGF2 水平在 PE 胎盘和 PAS 胎盘中均显著下降。这项研究表明，PE 和 PAS 胎盘中 DNA 甲基化和印记基因的表达均存在异常，PE 和 PAS 有不同的甲基化特征，这可能与其独特的发病机制有关。

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来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.