She Jiajie, Tan Kaifen, Liu Jie, Cao Shuo, Li Zengguang, Peng You, Xiao Zhuoyu, Diao Ruiying, Wang Liping
The First Affiliated Hospital of Shenzhen University, Reproductive Medicine Centre, Shenzhen Second People's Hospital, Shenzhen, China.
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Genet. 2022 Jun 8;13:861853. doi: 10.3389/fgene.2022.861853. eCollection 2022.
A growing number of studies have demonstrated that N6 methyladenine (mA) acts as an important role in the pathogenesis of reproductive diseases. Therefore, it is essential to profile the genome-wide mA modifications such as in spontaneous abortion. In this study, due to the trace of human villi during early pregnancy, we performed high-throughput sequencing in villous tissues from spontaneous abortion (SA group) and controls with induced abortion (normal group) in the first trimester. Based on meRIP-seq data, 18,568 mA peaks were identified. These mA peaks were mainly located in the coding region near the stop codon and were mainly characterized by AUGGAC and UGGACG motif. Compared with normal group, the SA group had 2,159 significantly upregulated mA peaks and 281 downregulated mA peaks. Biological function analyses revealed that differential mA-modified genes were mainly involved in the Hippo and Wnt signaling pathways. Based on the conjoint analysis of meRIP-seq and RNA-seq data, we identified thirty-five genes with differentially methylated mA peaks and synchronously differential expression. And these genes were mainly involved in the Wnt signaling pathway, phosphatase activity regulation, protein phosphatase inhibitor activity, and transcription inhibitor activity. This study is the first to profile the transcriptome-wide mA methylome in spontaneous abortion during early pregnancy, which provide novel insights into the pathogenesis and treatment of spontaneous abortion in the first trimester.
越来越多的研究表明，N6甲基腺嘌呤（mA）在生殖疾病的发病机制中起重要作用。因此，分析全基因组范围内的mA修饰，如自然流产中的修饰，至关重要。在本研究中，由于早孕期人绒毛量少，我们对孕早期自然流产组（SA组）和人工流产对照组（正常组）的绒毛组织进行了高通量测序。基于meRIP-seq数据，共鉴定出18568个mA峰。这些mA峰主要位于终止密码子附近的编码区，主要特征基序为AUGGAC和UGGACG。与正常组相比，SA组有2159个mA峰显著上调，281个mA峰下调。生物学功能分析显示，差异mA修饰的基因主要参与Hippo和Wnt信号通路。基于meRIP-seq和RNA-seq数据的联合分析，我们鉴定出35个具有差异甲基化mA峰且同步差异表达的基因。这些基因主要参与Wnt信号通路、磷酸酶活性调节、蛋白磷酸酶抑制活性和转录抑制活性。本研究首次分析了孕早期自然流产中转录组范围内的mA甲基化组，为孕早期自然流产的发病机制和治疗提供了新的见解。
