Transcriptome Sequencing of Adenomyosis Eutopic Endometrium: A New Insight into Its Pathophysiology
45 Pages Posted: 25 Oct 2018More...
Background: The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients, and provide a new insight into disease mechanisms at a transcriptome level.
Methods: RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. DEGs in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analyzed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system.
Findings: Totally, 373 genes were differentially expressed in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis indicated that IL-6 signaling and ERK/MAPK signaling was activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of C/EBPÎ² were associated with adenomyosis.
Interpretation: Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the link between C/EBPÎ² and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.
Funding Statement: This work is supported by the National Natural Science Foundation of China [NO. 81771551, 81501276 and 81401219], the Shanghai Municipal Commission of Science and Technology Program [NO. 17411972800 and 15411966700], the Shanghai Municipal Commission of Health and Family Planning [NO. 20154Y0039], the Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai [NO. 2018YQ39], the Shanghai Shenkang Hospital Development Center Clinical Science and Technology Innovation Project [NO. SHDC12017123], and the Combined Engineering and Medical Project of Shanghai Jiao Tong University [NO. YG2015MS41 and YG2017MS39].
Declaration of Interests: The authors have declared that no competing interests exist.
Ethics Approval Statement: The study protocols were approved by the Ethics Review Committee of IPMCH and conducted according to the Declaration of Helsinki Principles.
Keywords: Adenomyosis, Eutopic endometrium, RNA sequencing, C/EBPβ, DNA methylation
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