Serum levels of <scp>TSP</scp>‐1, <scp>NF</scp>‐κB and <scp>TGF</scp>‐β1 in polycystic ovarian syndrome (<scp>PCOS</scp>) patients in northern China suggest <scp>PCOS</scp> is associated with chronic inflammation

Liu, Meimei; Gao, Jiayin; Zhang, Yanhua; Li, Peiling; Wang, Hongli; Ren, Xiaopang; Li, Changmin

doi:10.1111/cen.12951

Cited by 72 publications

(42 citation statements)

References 32 publications

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“…The MAPK/ERK/p38 signaling pathway contributes to the regulation of inflammation and cytokine production 60,61 , and the dysregulation of inflammation-related molecules is associated with PCOS conditions [52][53][54]62 . Furthermore, like the activation of NFκB signaling that induces the transcriptional levels of inflammation-related gene expression in ovarian granulosa cells and in serum in PCOS patients 51,63 , our previous study has shown that the sustained metformin treatment markedly suppresses uterine inflammatory gene expression, especially the Il-6 and TNFα mRNAs that are associated with inhibition of nuclear NFκB translocation in PCOS-like rats 28 . Importantly, p38 can antagonize ERK1/2 signaling mediated by protein phosphatase 2A and consequently down-regulate inflammatory cytokine and chemokine production 61 , and the anti-inflammatory effects of MAPK/p38 are involved in the regulation of NFκB activity 60 .…”

Section: Commentmentioning

confidence: 96%

“…Importantly, chronic inflammation has been shown to be closely correlated to high inflammatory mediator production under PCOS conditions 2 . For example, there is a noticeable increase in the inflammatory cytokines such as IL-6 and TNFα in the peripheral circulation of PCOS patients 50,51 . Similarly, several studies by our laboratory and others have described increased gene expression of IL-6, TNFα, and Mcp-1 (CCL-2) in PCOS patient endometrium and the PCOS-like rat uterus 10,28,[52][53][54] .…”

Section: Commentmentioning

confidence: 99%

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Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Zhang

Feng

et al. 2017

Preprint

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Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

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Section: Commentmentioning

confidence: 96%

Section: Commentmentioning

confidence: 99%

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Zhang

Feng

et al. 2017

Preprint

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“…During the past two decades, emerging evidence has supported the essential contribution of AGE-RAGE to increased oxidative stress and inflammation. These processes perturbate the ovarian microenvironment and may cause infertility [2]. According to Merhiet et al [11], high follicular fluid sRAGE correlates with elevated ovarian reserve as measured by AMH [19].…”

Section: Discussionmentioning

confidence: 99%

“…PCOS is characterized by hyper-androgenism, polycystic ovaries, oligoovulation, and chronic anovulation [1]. Although the etiology of PCOS is unknown, imbalances between proinflammatory and anti-inflammatory pathways play a role in the pathogenesis of PCOS [2].…”

Section: Introductionmentioning

confidence: 99%

Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

Asan

Hao

Yang

et al. 2016

J Assist Reprod Genet

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Purpose To explore the relationships between the soluble receptor for advanced glycation endproducts (sRAGE) and the outcome parameters following in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) and investigate the protective effect of sRAGE in PCOS development regarding inflammation. Methods We conducted a prospective analysis of a subsample of 74 participants from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. We quantified sRAGE, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), interleukelin-6 (IL-6), and C-reactive protein (CPR) protein levels in the follicular fluid from 39 PCOS and 35 non-PCOS reproductive-age women. sRAGE and VEGF, TNF-α, IL-6, and CRP in follicular fluid aspirated without blood were measured by ELISA. Results sRAGE concentrations in the follicular fluid were significantly lower in the PCOS group compared to those in the control group, while VEGF, TNF-α, IL-6, and CRP concentrations were significantly higher in the PCOS group than in the control group (P < 0.05). sRAGE was significantly, inversely correlated with the total dose of gonadotropin (Gn) in the PCOS group undergoing IVF treatment (r = −0.451, P = 0.004). After adjusting for age and Gn dose (in international units used per cycle), sRAGE protein levels in the follicular fluid were significantly, inversely related to VEGF (r = −0.378, P = 0.018), TNF-α (r = −0.450, P = 0.004), IL-6 (r = −0.455, P = 0.004), and CRP (r = −0.375, P = 0.019). Conclusion sRAGE in the follicular fluid might exert a protective effect against the inflammatory action of PCOS development.

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“…Nuclear factor kappaB (NF-κB) is a crucial factor regulating in ammation, and following exogenous stimulation-free NF-κB translocates into the nucleus where it induces gene transcription to regulate and promote an in ammatory reaction [31]. It is reported that NF-κB in the PCOS groups weas signi cantly higher [32], indicating that PCOS maight be associated with chronic in ammation. In addition, GO classi cation also pointed to in ammatory response, upholding its importance in PCOS.…”

Section: Topological Characteristics Of Pclmn and The Cellular Localimentioning

confidence: 99%

Construction of Polycystic Ovarian Syndrome Related lncRNA-mRNA Network Based on ceRNA to Identify Functional lncRNAs in Polycystic Ovarian Syndrome

Zhai

2020

Preprint

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Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of childbearing age. Recent studies have shown that long non-coding RNA (lncRNA) played a vital role in the development of the PCOS. Competitive endogenous RNA (ceRNA), a novel interacting mechanism, in which lncRNA could interact with micro-RNAs (miRNA) and indirectly interact with mRNAs through competing interactions. However, the mechanism of ceRNA regulated by lncRNA in the PCOS was unclear. Results We constructed the global background network based on the assumed lncRNA-miRNA and miRNA-mRNA pairs, which were obtained from lncRNASNP, miRTarBase and StarBase database. Then we calculated differentially expressed genes of PCOS using the data of GSE95728. PCOS related lncRNA-mRNA network (PCLMN) was constructed by hypergeometric test, including 41 mRNA nodes, 41 lncRNA nodes and 203 edges. Topological analyses was performed to determine the crucial lncRNAs with the highest centroid. We further identified the subcellular localization, performed functional module analyses and identified putative transfer factors of the key lncRNAs. Functional enrichment analyses were performed by GO classification and KEGG pathway analyses. Finally, 3 key lncRNAs(LINC00667, H19, AC073172.1) and their ceRNA sub-networks, which were involved in NF-kB signaling pathway, inflammatory, apoptotic and immune-related processes, had been found as the potential PCOS related disease genes. Conclusions Based on the result above, we speculate that LINC00667, H19, AC073172.1 and their ceRNA sub-networks played an crucial role in PCOS. All these results can help us discover the molecular mechanism and offer new predictive biomarkers for PCOS.

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Serum levels of TSP‐1, NF‐κB and TGF‐β1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation

Abstract: These results support the association between PCOS and chronic inflammation.

Cited by 72 publications

References 32 publications

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

Construction of Polycystic Ovarian Syndrome Related lncRNA-mRNA Network Based on ceRNA to Identify Functional lncRNAs in Polycystic Ovarian Syndrome

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Serum levels of TSP‐1, NF‐κB and TGF‐β1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation

Abstract: These results support the association between PCOS and chronic inflammation.

Cited by 72 publications

References 32 publications

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

Construction of Polycystic Ovarian Syndrome&nbsp;Related&nbsp;lncRNA-mRNA Network&nbsp;Based on ceRNA to Identify Functional lncRNAs&nbsp;in Polycystic Ovarian Syndrome

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Construction of Polycystic Ovarian Syndrome Related lncRNA-mRNA Network Based on ceRNA to Identify Functional lncRNAs in Polycystic Ovarian Syndrome