Exploration of molecular features of PCOS with different androgen levels and immune-related prognostic biomarkers associated with implantation failure

Gao, Qinyu; Ma, Cong; Meng, Shuyu; Wang, Guanxiong; Xing, Qinghe; Xu, Yuping; He, Xiaojin; Wang, Tianjuan; Cao, Yunxia

doi:10.3389/fendo.2022.946504

Cited by 5 publications

(3 citation statements)

References 79 publications

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“…Consistent with previous studies ( 48 , 49 ), our data showed that the common gene population mainly enriched in the activation pathways of immune cells like T cells, NK cells, macrophages, and neutrophils. These results hinted us the high level of immunity in PCOS and RIF patients and prompted us to further investigate which immune cells are abnormal in the two diseases.…”

Section: Discussionsupporting

confidence: 92%

Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning

Chen

Yang

et al. 2023

Front. Immunol.

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Polycystic ovary syndrome (PCOS) is a complex endocrine metabolic disorder that affects 5–10% of women of reproductive age. The endometrium of women with PCOS has altered immune cells resulting in chronic low-grade inflammation, which attribute to recurrent implantation failure (RIF). In this study, we obtained three PCOS and RIF datasets respectively from the Gene Expression Omnibus (GEO) database. By analyzing differentially expressed genes (DEGs) and module genes using weighted gene co-expression networks (WGCNA), functional enrichment analysis, and three machine learning algorithms, we identified twelve diseases shared genes, and two diagnostic genes, including GLIPR1 and MAMLD1. PCOS and RIF validation datasets were assessed using the receiver operating characteristic (ROC) curve, and ideal area under the curve (AUC) values were obtained for each disease. Besides, we collected granulosa cells from healthy and PCOS infertile women, and endometrial tissues of healthy and RIF patients. RT-PCR was used to validate the reliability of GLIPR1 and MAMLD1. Furthermore, we performed gene set enrichment analysis (GSEA) and immune infiltration to explore the underlying mechanism of PCOS and RIF cooccurrence. Through the functional enrichment of twelve shared genes and two diagnostic genes, we found that both PCOS and RIF patients had disturbances in metabolites related to the TCA cycle, which eventually led to the massive activation of immune cells.

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Section: Discussionsupporting

confidence: 92%

Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning

Chen

Yang

et al. 2023

Front. Immunol.

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“…Studies have stated that hormone abnormalities in PCOS can overstimulate the immune system, and concurrently, inflammatory cell infiltration aggravates ovarian dysfunction and metabolic disorders [ 35 , 36 ]. High infiltrating abundances of macrophages [ 37 ], neutrophils, activated dendritic cells [ 38 ], and eosinophils [ 39 , 40 ] were observed in PCOS. Since chronic low-level inflammation plays a critical role in PCOS [ 41 ], we investigated and compared the immune infiltration and cytokine levels in different groups.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in Polycystic Ovary Syndrome (PCOS)

2023

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Background Polycystic ovary syndrome (PCOS) is a multisystem-related disease whose pathophysiology is still unclear. Several regulators of N6-methyladenosine (m6A) modification were confirmed to play a regulatory role in PCOS. Nonetheless, the roles of m6A regulators in PCOS are not fully demonstrated. Materials and methods Four mRNA expression profiling microarrays were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed m6A regulators between PCOS and normal patients were identified by R software. A random forest modal and nomogram were developed to assess the relationship between m6A regulators and the occurrence risk of PCOS. A consensus clustering method was utilized to distinctly divide PCOS patients into two m6A subtypes (m6A cluster A/B). The patterns of differential expression and immune infiltration were explored between the two m6A clusters. Results In this study, 22 significant m6A regulators were identified between healthy controls and PCOS patients. The random forest model determined three optimal m6A regulators which are related to the occurrence risk of PCOS, including YTHDF1, RBM15 and METTL14. A nomogram was established based on these genes, and its predictive reliability was validated by decision curve analysis. The consensus clustering algorithm distinctly divided PCOS cases into two m6A subtypes. The ssGSEA algorithm found that the immune infiltration was markedly enriched in m6A cluster B than in cluster A. The m6A-pattern related differentially expressed genes (DEGs) of the two m6A subtypes were demonstrated by differential expression analysis. We found that they were enriched in immune-related genes and various infection pathways. Based on the m6A-pattern related DEGs, the PCOS patients were classified into two m6A-pattern related genomic subtypes (gene clusters A and B). Conclusions The present study provided evidence concerning the different modification patterns of m6A regulators in PCOS compared with normal patients. This study will help clarify the overall impact of m6A modification patterns and related immune infiltration on PCOS.

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“…The true predisposing factors for OSA in women with PCOS may be IR and obesity (152). Obesity/insulin-resistance may be the main cause of sleep apnea, which in turn may accelerate these metabolic abnormalities because of the gradual rise of cytokines, such as IL-6 and TNF-a (159).…”

Section: Pcos-related Immune Dysregulation In the Other Systemmentioning

confidence: 99%

Dysregulation of immune response in PCOS organ system

2023

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Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder affecting women, which can lead to infertility. Infertility, obesity, hirsutism, acne, and irregular menstruation are just a few of the issues that PCOS can be linked to. PCOS has a complicated pathophysiology and a range of clinical symptoms. Chronic low-grade inflammation is one of the features of PCOS. The inflammatory environment involves immune and metabolic disturbances. Numerous organ systems across the body, in addition to the female reproductive system, have been affected by the pathogenic role of immunological dysregulation in PCOS in recent years. Insulin resistance and hyperandrogenism are associated with immune cell dysfunction and cytokine imbalance. More importantly, obesity is also involved in immune dysfunction in PCOS, leading to an inflammatory environment in women with PCOS. Hormone, obesity, and metabolic interactions contribute to the pathogenesis of PCOS. Hormone imbalance may also contribute to the development of autoimmune diseases. The aim of this review is to summarize the pathophysiological role of immune dysregulation in various organ systems of PCOS patients and provide new ideas for systemic treatment of PCOS in the future.

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Exploration of molecular features of PCOS with different androgen levels and immune-related prognostic biomarkers associated with implantation failure

Cited by 5 publications

References 79 publications

Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning

Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning

N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in Polycystic Ovary Syndrome (PCOS)

Dysregulation of immune response in PCOS organ system

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