Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility
Abstract Background Polycystic ovarian syndrome (PCOS) is a leading cause of infertility and metabolic dysfunction in women, characterized by hyperandrogenism, anovulation, and insulin resistance. Cumulus cells play a crucial role in folliculogenesis and oocyte maturation, necessitating a deeper und...
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| Language: | English |
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SpringerOpen
2025-08-01
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| Series: | Middle East Fertility Society Journal |
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| Online Access: | https://doi.org/10.1186/s43043-025-00241-w |
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| author | Akeem Babatunde Sikiru Nurulfiza Mat Isa Kasim Sakran Abass Muibat Adesola Adeniran Stephen Sunday Acheneje Egena Karimot Akinola |
| author_facet | Akeem Babatunde Sikiru Nurulfiza Mat Isa Kasim Sakran Abass Muibat Adesola Adeniran Stephen Sunday Acheneje Egena Karimot Akinola |
| author_sort | Akeem Babatunde Sikiru |
| collection | DOAJ |
| description | Abstract Background Polycystic ovarian syndrome (PCOS) is a leading cause of infertility and metabolic dysfunction in women, characterized by hyperandrogenism, anovulation, and insulin resistance. Cumulus cells play a crucial role in folliculogenesis and oocyte maturation, necessitating a deeper understanding of their molecular alterations impact in PCOS. Method This study investigates transcriptomic differences in cumulus cells between PCOS and non-PCOS women using high-throughput RNA sequencing data obtained from the NCBI Gene Expression Omnibus (GEO) database (accession number: GSE277906). The RNA sequencing data from 23 PCOS and 17 non-PCOS women were analyzed to identify differentially expressed genes (DEGs) using R-based computational pipelines. Results Differential gene expression analysis identified 3245 significantly dysregulated genes, comprising 1723 upregulated and 1522 downregulated genes in PCOS samples. Functional enrichment analysis revealed that key DEGs (CDH5, CLEC4D, and GNAT1) were associated with follicular development, insulin signaling, and immune response. Gene Set Enrichment Analysis (GSEA) further identified dysregulation in metabolic and reproductive pathways, including ribonucleoprotein complex biogenesis and vascular endothelial growth factor (VEGF) signaling. Conclusion This study highlights that altered gene expression in cumulus cells may impair oocyte competence, potentially influencing fertility outcomes in PCOS patients. GNAT1, previously linked to diabetes, emerged as a novel gene potentially involved in PCOS pathophysiology. However, these findings are derived from a single-center dataset which requires experimental validation. Future studies should incorporate qRT-PCR validation and functional assays in larger and ethically diverse cohorts as means for development of targeted therapeutic interventions to mitigate the reproductive consequences of PCOS. |
| format | Article |
| id | doaj-art-e7c2ec5031394e2bb3dff57ce1258b66 |
| institution | Kabale University |
| issn | 2090-3251 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Middle East Fertility Society Journal |
| spelling | doaj-art-e7c2ec5031394e2bb3dff57ce1258b662025-08-20T03:45:45ZengSpringerOpenMiddle East Fertility Society Journal2090-32512025-08-0130111210.1186/s43043-025-00241-wTranscriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertilityAkeem Babatunde Sikiru0Nurulfiza Mat Isa1Kasim Sakran Abass2Muibat Adesola Adeniran3Stephen Sunday Acheneje Egena4Karimot Akinola5Molecular, Cellular and Integrative Physiology Laboratory (MCIP), Department of Animal Science, Federal University of Agriculture ZuruLaboratory of Vaccines and Biomolecules (VacBio), Institute of Biosciences, Universiti Putra MalaysiaDepartment of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of KirkukDepartment of Obstetrics and Gynaecology, Faculty of Health Sciences, College of Clinical Sciences, Ladoke Akintola University of TechnologyDepartment of Animal Production, School of Food and Agriculture Technology, Federal University of TechnologyDepartment of Public Health, Fountain UniversityAbstract Background Polycystic ovarian syndrome (PCOS) is a leading cause of infertility and metabolic dysfunction in women, characterized by hyperandrogenism, anovulation, and insulin resistance. Cumulus cells play a crucial role in folliculogenesis and oocyte maturation, necessitating a deeper understanding of their molecular alterations impact in PCOS. Method This study investigates transcriptomic differences in cumulus cells between PCOS and non-PCOS women using high-throughput RNA sequencing data obtained from the NCBI Gene Expression Omnibus (GEO) database (accession number: GSE277906). The RNA sequencing data from 23 PCOS and 17 non-PCOS women were analyzed to identify differentially expressed genes (DEGs) using R-based computational pipelines. Results Differential gene expression analysis identified 3245 significantly dysregulated genes, comprising 1723 upregulated and 1522 downregulated genes in PCOS samples. Functional enrichment analysis revealed that key DEGs (CDH5, CLEC4D, and GNAT1) were associated with follicular development, insulin signaling, and immune response. Gene Set Enrichment Analysis (GSEA) further identified dysregulation in metabolic and reproductive pathways, including ribonucleoprotein complex biogenesis and vascular endothelial growth factor (VEGF) signaling. Conclusion This study highlights that altered gene expression in cumulus cells may impair oocyte competence, potentially influencing fertility outcomes in PCOS patients. GNAT1, previously linked to diabetes, emerged as a novel gene potentially involved in PCOS pathophysiology. However, these findings are derived from a single-center dataset which requires experimental validation. Future studies should incorporate qRT-PCR validation and functional assays in larger and ethically diverse cohorts as means for development of targeted therapeutic interventions to mitigate the reproductive consequences of PCOS.https://doi.org/10.1186/s43043-025-00241-wPCOSCumulus cellsGNAT1Oocyte competence, Infertility |
| spellingShingle | Akeem Babatunde Sikiru Nurulfiza Mat Isa Kasim Sakran Abass Muibat Adesola Adeniran Stephen Sunday Acheneje Egena Karimot Akinola Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility Middle East Fertility Society Journal PCOS Cumulus cells GNAT1 Oocyte competence, Infertility |
| title | Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility |
| title_full | Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility |
| title_fullStr | Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility |
| title_full_unstemmed | Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility |
| title_short | Transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in PCOS-related infertility |
| title_sort | transcriptomic profiling of cumulus cells reveals dysregulated genes and pathways in pcos related infertility |
| topic | PCOS Cumulus cells GNAT1 Oocyte competence, Infertility |
| url | https://doi.org/10.1186/s43043-025-00241-w |
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