Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA
Abstract Background Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis i...
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BMC
2024-11-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-024-01542-w |
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| author | Xueying Cui Xiaocan Lei Tao Huang Xueyan Mao Zhiwei Shen Xiuli Yang Wanting Peng Jingjing Yu Shun Zhang Peng Huo |
| author_facet | Xueying Cui Xiaocan Lei Tao Huang Xueyan Mao Zhiwei Shen Xiuli Yang Wanting Peng Jingjing Yu Shun Zhang Peng Huo |
| author_sort | Xueying Cui |
| collection | DOAJ |
| description | Abstract Background Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis in granulosa cells (GCs), and its potential contribution to follicular dysregulation. Methods Herein, Follicular follicular fluid (FF) samples were collected from six patients with PCOS and six healthy controls undergoing in vitro fertilization-embryo transfer. The isolated extracellular vesicles were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Additionally, miRNA sequencing was performed to identify differentially expressed microRNAs, and their functions were analyzed through transcriptomics. The In vitro effects of miR-34a-5p on glycolysis, cell proliferation, and apoptosis were assessed in human ovarian granulosa tumour cell line (KGN cells). Targets of miR-34a-5p were identified by dual-luciferase reporter assays, and quantitative real-time polymerase chain reaction and western blotting were performed to determine gene and protein expression. Results The level of miR-34a-5p in FF-derived extracellular vesicles derived from patients with PCOS was significantly higher than that of the control group. Transcriptomic analysis highlighted miR-34a-5p as a key regulator of glycolysis and apoptosis. Furthermore, in vitro analysis showed that miR-34a-5p targeted lactate dehydrogenase A (LDHA), inhibited glycolysis, reduced energy supply to GCs, and promoted apoptosis of KGN cells. Conversely, miR-34a-5p inhibition restored glycolysis function and cell viability. Conclusion The findings of this study show that miR-34a-5p mediates GC apoptosis in PCOS by targeting LDHA and inhibiting glycolysis, suggesting its crucial role in PCOS pathophysiology, and offering potential therapeutic targets for improving follicular development and fertility outcomes in patients with PCOS. Further research is needed to explore the clinical implications of miR-34a-5p and its use as a biomarker for early diagnosis and prognosis of PCOS. |
| format | Article |
| id | doaj-art-a50b9cde44ae4e7b8b0287ab293903e2 |
| institution | OA Journals |
| issn | 1757-2215 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-a50b9cde44ae4e7b8b0287ab293903e22025-08-20T02:20:06ZengBMCJournal of Ovarian Research1757-22152024-11-0117111310.1186/s13048-024-01542-wFollicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHAXueying Cui0Xiaocan Lei1Tao Huang2Xueyan Mao3Zhiwei Shen4Xiuli Yang5Wanting Peng6Jingjing Yu7Shun Zhang8Peng Huo9Department of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical UniversityClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, University of South ChinaThe Second Affiliated Hospital of Guilin Medical UniversityClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, University of South ChinaClinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, University of South ChinaDepartment of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical UniversityGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical UniversityGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical UniversityDepartment of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical UniversityGuangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical UniversityAbstract Background Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis in granulosa cells (GCs), and its potential contribution to follicular dysregulation. Methods Herein, Follicular follicular fluid (FF) samples were collected from six patients with PCOS and six healthy controls undergoing in vitro fertilization-embryo transfer. The isolated extracellular vesicles were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Additionally, miRNA sequencing was performed to identify differentially expressed microRNAs, and their functions were analyzed through transcriptomics. The In vitro effects of miR-34a-5p on glycolysis, cell proliferation, and apoptosis were assessed in human ovarian granulosa tumour cell line (KGN cells). Targets of miR-34a-5p were identified by dual-luciferase reporter assays, and quantitative real-time polymerase chain reaction and western blotting were performed to determine gene and protein expression. Results The level of miR-34a-5p in FF-derived extracellular vesicles derived from patients with PCOS was significantly higher than that of the control group. Transcriptomic analysis highlighted miR-34a-5p as a key regulator of glycolysis and apoptosis. Furthermore, in vitro analysis showed that miR-34a-5p targeted lactate dehydrogenase A (LDHA), inhibited glycolysis, reduced energy supply to GCs, and promoted apoptosis of KGN cells. Conversely, miR-34a-5p inhibition restored glycolysis function and cell viability. Conclusion The findings of this study show that miR-34a-5p mediates GC apoptosis in PCOS by targeting LDHA and inhibiting glycolysis, suggesting its crucial role in PCOS pathophysiology, and offering potential therapeutic targets for improving follicular development and fertility outcomes in patients with PCOS. Further research is needed to explore the clinical implications of miR-34a-5p and its use as a biomarker for early diagnosis and prognosis of PCOS.https://doi.org/10.1186/s13048-024-01542-wPolycystic ovary syndromeMiR-34a-5pQPCRLDHA |
| spellingShingle | Xueying Cui Xiaocan Lei Tao Huang Xueyan Mao Zhiwei Shen Xiuli Yang Wanting Peng Jingjing Yu Shun Zhang Peng Huo Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA Journal of Ovarian Research Polycystic ovary syndrome MiR-34a-5p QPCR LDHA |
| title | Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA |
| title_full | Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA |
| title_fullStr | Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA |
| title_full_unstemmed | Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA |
| title_short | Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA |
| title_sort | follicular fluid derived extracellular vesicles mir 34a 5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting ldha |
| topic | Polycystic ovary syndrome MiR-34a-5p QPCR LDHA |
| url | https://doi.org/10.1186/s13048-024-01542-w |
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