Regulation of RNA splicing in endometrial tissue and its association with endometriosis

Summary: The endometrium, essential for reproduction, undergoes cyclical shedding, remodeling, and regeneration. Using a large endometrial transcriptomic dataset (n = 206), we identified RNA splicing and transcript isoform-level changes across the menstrual cycle and in endometriosis, findings not s...

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Main Authors: Fei Yang, Ting Qi, Allan F. McRae, Peter A.W. Rogers, Grant W. Montgomery, Sally Mortlock
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225014683
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author Fei Yang
Ting Qi
Allan F. McRae
Peter A.W. Rogers
Grant W. Montgomery
Sally Mortlock
author_facet Fei Yang
Ting Qi
Allan F. McRae
Peter A.W. Rogers
Grant W. Montgomery
Sally Mortlock
author_sort Fei Yang
collection DOAJ
description Summary: The endometrium, essential for reproduction, undergoes cyclical shedding, remodeling, and regeneration. Using a large endometrial transcriptomic dataset (n = 206), we identified RNA splicing and transcript isoform-level changes across the menstrual cycle and in endometriosis, findings not seen in gene-level analyses. Transcriptomic differences were most pronounced in the mid-secretory (receptive) phase in endometriosis samples. By integrating genotype data, we found evidence of cis-genetic effects on splicing in endometrium, identifying 3,296 splicing quantitative trait loci (sQTLs) with the majority of genes with sQTLs (67.5%) not discovered in the gene level eQTLs analysis, indicating the splicing-specific effects. Integrating the sQTLs with the endometriosis genome-wide association study (GWAS) data, we identified two genes (GREB1 and WASHC3) that were significantly associated with endometriosis risk through genetically regulated splicing events. Overall, this study detected transcript isoform-level and RNA splicing level specific changes, providing insights into the dynamic changes in transcriptomic regulation in endometrium and its association with endometriosis.
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spelling doaj-art-db87ff5e6b9b4c20a3f3d0be254c69472025-08-20T04:00:55ZengElsevieriScience2589-00422025-09-0128911320710.1016/j.isci.2025.113207Regulation of RNA splicing in endometrial tissue and its association with endometriosisFei Yang0Ting Qi1Allan F. McRae2Peter A.W. Rogers3Grant W. Montgomery4Sally Mortlock5The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, ChinaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaUniversity of Melbourne Department of Obstetrics and Gynaecology, and Gynaecology Research Centre, Royal Women’s Hospital, Parkville, VIC 3052, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; Australian Women and Girls’ Health Research Centre, School of Public Health, University of Queensland, Herston, QLD 4006, Australia; Corresponding authorSummary: The endometrium, essential for reproduction, undergoes cyclical shedding, remodeling, and regeneration. Using a large endometrial transcriptomic dataset (n = 206), we identified RNA splicing and transcript isoform-level changes across the menstrual cycle and in endometriosis, findings not seen in gene-level analyses. Transcriptomic differences were most pronounced in the mid-secretory (receptive) phase in endometriosis samples. By integrating genotype data, we found evidence of cis-genetic effects on splicing in endometrium, identifying 3,296 splicing quantitative trait loci (sQTLs) with the majority of genes with sQTLs (67.5%) not discovered in the gene level eQTLs analysis, indicating the splicing-specific effects. Integrating the sQTLs with the endometriosis genome-wide association study (GWAS) data, we identified two genes (GREB1 and WASHC3) that were significantly associated with endometriosis risk through genetically regulated splicing events. Overall, this study detected transcript isoform-level and RNA splicing level specific changes, providing insights into the dynamic changes in transcriptomic regulation in endometrium and its association with endometriosis.http://www.sciencedirect.com/science/article/pii/S2589004225014683health sciencesbiological sciencesmolecular biologydevelopmental biologybiology of human developmentcomplex system biology
spellingShingle Fei Yang
Ting Qi
Allan F. McRae
Peter A.W. Rogers
Grant W. Montgomery
Sally Mortlock
Regulation of RNA splicing in endometrial tissue and its association with endometriosis
iScience
health sciences
biological sciences
molecular biology
developmental biology
biology of human development
complex system biology
title Regulation of RNA splicing in endometrial tissue and its association with endometriosis
title_full Regulation of RNA splicing in endometrial tissue and its association with endometriosis
title_fullStr Regulation of RNA splicing in endometrial tissue and its association with endometriosis
title_full_unstemmed Regulation of RNA splicing in endometrial tissue and its association with endometriosis
title_short Regulation of RNA splicing in endometrial tissue and its association with endometriosis
title_sort regulation of rna splicing in endometrial tissue and its association with endometriosis
topic health sciences
biological sciences
molecular biology
developmental biology
biology of human development
complex system biology
url http://www.sciencedirect.com/science/article/pii/S2589004225014683
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AT peterawrogers regulationofrnasplicinginendometrialtissueanditsassociationwithendometriosis
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