Identification and Validation of Genes Involved in Immune and Ferroptosis in Polycystic Ovarian Syndrome Using Bioinformatics and Experimental Approach
4 affiliations
- 1Department of Gynecological Outpatient, Yunnan Provincial Hospital of Chinese Medicine
- 2Department of Rehabilitation, Yunnan University of Traditional Chinese Medicine Second Affiliated Hospital
- 3The Second Clinical Medical College of Yunnan, University of Chinese Medicine
- 4Department of Traditional Chinese Medicine, Kunming Maternal and Child Health Hospital
Abstract
Background Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disease. This study aimed to investigate the synergistic role of immune dysregulation and ferroptosis during the pathogenesis of PCOS. Methods Through integrating multiple Gene Expression Omnibus (GEO) datasets, differentially expressed genes (DEGs) were screened and subjected to functional enrichment analysis; weighted gene co‑expression network analysis combined with LASSO, RandomForest, and support vector machine‑recursive feature elimination algorithms were employed to identify key candidate genes; in vitro, human ovarian granulosa cells (KGN) were treated with dihydrotestosterone (DHT), NNMT expression was regulated via lentiviral vectors together with ferroptosis inhibitor intervention, and cell viability, cytotoxicity, and ferroptosis‑related indicators were examined; in vivo, a PCOS mouse model was established using dehydroepiandrosterone, and ovarian pathology, hormone levels, as well as molecular expression of the ferroptosis pathway were analyzed. Results DEGs in PCOS were significantly enriched in immune response and ferroptosis pathways. Twelve candidate genes were identified through screening multiple GEO datasets and demonstrated diagnostic potential. DHT induced ferroptosis in KGN cells by upregulating NNMT, manifesting as reduced cell viability, increased LDH release, accompanied by Fe²⁺ accumulation, enhanced lipid peroxidation, downregulation of SLC7A11/GPX4, and upregulation of ACSL4. This process could be partially reversed by ferroptosis inhibitors. Knockdown of NNMT effectively alleviated the DHT‑induced ferroptosis phenotype. Ovaries from PCOS mice exhibited typical pathological alterations, concurrent with elevated NNMT expression and abnormal activation of the ferroptosis pathway. Conclusion This study has uncovered novel mechanisms underlying the development and progression of PCOS, offering potential targets for its diagnosis and treatment.
Related
- Comprehensive identification of lactate metabolism-related genes in recurrent spontaneous abortion : An observational study integrating bioinformatics and experimental validation
- Identification and validation of CCL28 and CCL5 as chemokine biomarkers and pro-inflammatory mediators in acute pancreatitis: an integrated bioinformatics and experimental study
- Identification of candidate selenium-associated transcriptomic biomarkers in chronic obstructive pulmonary disease: an integrated bioinformatics and expression validation study
- Identification and validation of feature genes using a ferroptosis-informed analytical framework in medulloblastoma
- Unraveling the therapeutic mechanisms of placenta hominis for polycystic ovary syndrome through network pharmacology, molecular docking, and experimental validation
BibTeX
@article{chen2026identification,
title = {{Identification and Validation of Genes Involved in Immune and Ferroptosis in Polycystic Ovarian Syndrome Using Bioinformatics and Experimental Approach}},
author = {Yang Chen and Liwei Xing and Zhe He and Xiaoqi Wang and Yujing Chen and Xiaowei Yuan and Rong Zhao},
journal = {Biological Procedures Online},
year = {2026},
month = jul,
doi = {10.1186/s12575-026-00355-z},
url = {https://doi.org/10.1186/s12575-026-00355-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Identification and Validation of Genes Involved in Immune and Ferroptosis in Polycystic Ovarian Syndrome Using Bioinformatics and Experimental Approach
AU - Yang Chen
AU - Liwei Xing
AU - Zhe He
AU - Xiaoqi Wang
AU - Yujing Chen
AU - Xiaowei Yuan
AU - Rong Zhao
PY - 2026
DA - 2026/07/01
JO - Biological Procedures Online
DO - 10.1186/s12575-026-00355-z
UR - https://doi.org/10.1186/s12575-026-00355-z
AB - Background Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disease. This study aimed to investigate the synergistic role of immune dysregulation and ferroptosis during the pathogenesis of PCOS. Methods Through integrating multiple Gene Expression Omnibus (GEO) datasets, differentially expressed genes (DEGs) were screened and subjected to functional enrichment analysis; weighted gene co‑expression network analysis combined with LASSO, RandomForest, and support vector machine‑recursive feature elimination algorithms were employed to identify key candidate genes; in vitro, human ovarian granulosa cells (KGN) were treated with dihydrotestosterone (DHT), NNMT expression was regulated via lentiviral vectors together with ferroptosis inhibitor intervention, and cell viability, cytotoxicity, and ferroptosis‑related indicators were examined; in vivo, a PCOS mouse model was established using dehydroepiandrosterone, and ovarian pathology, hormone levels, as well as molecular expression of the ferroptosis pathway were analyzed. Results DEGs in PCOS were significantly enriched in immune response and ferroptosis pathways. Twelve candidate genes were identified through screening multiple GEO datasets and demonstrated diagnostic potential. DHT induced ferroptosis in KGN cells by upregulating NNMT, manifesting as reduced cell viability, increased LDH release, accompanied by Fe²⁺ accumulation, enhanced lipid peroxidation, downregulation of SLC7A11/GPX4, and upregulation of ACSL4. This process could be partially reversed by ferroptosis inhibitors. Knockdown of NNMT effectively alleviated the DHT‑induced ferroptosis phenotype. Ovaries from PCOS mice exhibited typical pathological alterations, concurrent with elevated NNMT expression and abnormal activation of the ferroptosis pathway. Conclusion This study has uncovered novel mechanisms underlying the development and progression of PCOS, offering potential targets for its diagnosis and treatment.
SN - 1480-9222
ER -