N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility

Endometriosis (EMS) is a chronic inflammatory disease frequently associated with infertility. N6-methyladenosine (m6A) methylation, the most common form of methylation in eukaryotic mRNAs, has gained attention in the study of female reproductive diseases, including EMS and infertility. This study a...

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Main Authors: Yalun He, Jie Ding, Tonglin Bai, Yangshuo Li, Xiaolan Liang, Yiming Chen, Yi Lin, Wen Cheng, Chaoqin Yu
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2024-12-01
Series:Biomolecules & Biomedicine
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Online Access:https://www.bjbms.org/ojs/index.php/bjbms/article/view/11311
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author Yalun He
Jie Ding
Tonglin Bai
Yangshuo Li
Xiaolan Liang
Yiming Chen
Yi Lin
Wen Cheng
Chaoqin Yu
author_facet Yalun He
Jie Ding
Tonglin Bai
Yangshuo Li
Xiaolan Liang
Yiming Chen
Yi Lin
Wen Cheng
Chaoqin Yu
author_sort Yalun He
collection DOAJ
description Endometriosis (EMS) is a chronic inflammatory disease frequently associated with infertility. N6-methyladenosine (m6A) methylation, the most common form of methylation in eukaryotic mRNAs, has gained attention in the study of female reproductive diseases, including EMS and infertility. This study aimed to investigate the role of m6A regulators in EMS-related infertility. To begin, specific m6A regulators were identified by analyzing the GSE120103 dataset, followed by receiver operating characteristic (ROC) curve analysis. A nomogram model was then constructed, and unsupervised clustering of m6A regulators was performed to identify distinct m6A molecular clusters. Functional enrichment analysis of differentially expressed genes (DEGs) between these clusters, along with immune cell infiltration analysis, was subsequently conducted. In addition, the single-cell dataset GSE214411 was analyzed to explore the role of m6A regulators in various cell types. Finally, clinical samples were collected, and immunohistochemistry analysis was performed. The study identified seven key m6A regulators with significant diagnostic value for EMS-related infertility and two distinct m6A molecular clusters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs between the clusters revealed that m6A clustering was strongly associated with immune pathways. Immune cell infiltration analysis further demonstrated that the expression levels of m6A regulators had a notable impact on immune cell infiltration. Single-cell analysis revealed that HNRNPA2B1 and HNRNPC were significantly elevated in endometrial immune cells from infertile EMS patients but notably decreased in stromal cells. Immunohistochemical staining confirmed that HNRNPA2B1 and HNRNPC expression levels were significantly higher in the eutopic endometrium of fertile women compared to ovarian EMS patients. These findings suggest that m6A regulators play critical roles in the development and progression of EMS-related infertility. Notably, HNRNPA2B1 and HNRNPC may serve as potential biomarkers for this condition.
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spelling doaj-art-d75c797632d54fdf861eec04220f14f32025-01-06T16:39:07ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-12-0110.17305/bb.2024.11311N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertilityYalun He0Jie Ding1Tonglin Bai2Yangshuo Li3Xiaolan Liang4Yiming Chen5Yi Lin6Wen Cheng7Chaoqin Yu8Department of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Physiotherapy of Traditional Chinese Medicine, Beidaihe Rehabilitation and Recuperation Center, The People's Liberation Army Joint Logistic Support Force, Qinhuangdao, ChinaDepartment of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Reproductive Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Medical University, Shanghai, China; Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Medical University, Shanghai, China Endometriosis (EMS) is a chronic inflammatory disease frequently associated with infertility. N6-methyladenosine (m6A) methylation, the most common form of methylation in eukaryotic mRNAs, has gained attention in the study of female reproductive diseases, including EMS and infertility. This study aimed to investigate the role of m6A regulators in EMS-related infertility. To begin, specific m6A regulators were identified by analyzing the GSE120103 dataset, followed by receiver operating characteristic (ROC) curve analysis. A nomogram model was then constructed, and unsupervised clustering of m6A regulators was performed to identify distinct m6A molecular clusters. Functional enrichment analysis of differentially expressed genes (DEGs) between these clusters, along with immune cell infiltration analysis, was subsequently conducted. In addition, the single-cell dataset GSE214411 was analyzed to explore the role of m6A regulators in various cell types. Finally, clinical samples were collected, and immunohistochemistry analysis was performed. The study identified seven key m6A regulators with significant diagnostic value for EMS-related infertility and two distinct m6A molecular clusters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs between the clusters revealed that m6A clustering was strongly associated with immune pathways. Immune cell infiltration analysis further demonstrated that the expression levels of m6A regulators had a notable impact on immune cell infiltration. Single-cell analysis revealed that HNRNPA2B1 and HNRNPC were significantly elevated in endometrial immune cells from infertile EMS patients but notably decreased in stromal cells. Immunohistochemical staining confirmed that HNRNPA2B1 and HNRNPC expression levels were significantly higher in the eutopic endometrium of fertile women compared to ovarian EMS patients. These findings suggest that m6A regulators play critical roles in the development and progression of EMS-related infertility. Notably, HNRNPA2B1 and HNRNPC may serve as potential biomarkers for this condition. https://www.bjbms.org/ojs/index.php/bjbms/article/view/11311N6-methyladenosinem6AendometriosisEMSimmune systeminfertility
spellingShingle Yalun He
Jie Ding
Tonglin Bai
Yangshuo Li
Xiaolan Liang
Yiming Chen
Yi Lin
Wen Cheng
Chaoqin Yu
N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
Biomolecules & Biomedicine
N6-methyladenosine
m6A
endometriosis
EMS
immune system
infertility
title N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
title_full N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
title_fullStr N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
title_full_unstemmed N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
title_short N6-methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
title_sort n6 methyladenosine methylation regulators can serve as potential biomarkers for endometriosis related infertility
topic N6-methyladenosine
m6A
endometriosis
EMS
immune system
infertility
url https://www.bjbms.org/ojs/index.php/bjbms/article/view/11311
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