scholarly journals Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

2021 ◽  
Vol 22 (8) ◽  
pp. 3923
Author(s):  
Siarhei A. Dabravolski ◽  
Nikita G. Nikiforov ◽  
Ali H. Eid ◽  
Ludmila V. Nedosugova ◽  
Antonina V. Starodubova ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Causative Role ◽  
Mitochondrial Dysfunctions ◽  
Mtdna Mutations ◽  
Targeted Treatments ◽  
Tnf Α ◽  
Novel Biomarkers

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

scholarly journals Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 100
Author(s):  
Abhaya Krishnan ◽  
Sridhar Muthusami ◽  
Loganayaki Periyasamy ◽  
Jone A. Stanley ◽  
Vasudevan Gopalakrishnan ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Model System ◽  
Reproductive Age ◽  
Albino Rats ◽  
Low Grade ◽  
Tnf Α ◽  
Inflammatory State

Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.

scholarly journals The polycystic ovarian syndrome and chronic inflammation: The role of Toll-like receptors

2018 ◽  
Vol 72 ◽  
pp. 1199-1207 ◽  
Author(s):  
Maja Jończyk ◽  
Justyna Kuliczkowska-Płaksej ◽  
Agata Mierzwicka ◽  
Marek Bolanowski
Keyword(s):  
Chronic Inflammation ◽  
Pancreatic Beta Cells ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Cell Types ◽  
Specific Gene ◽  
Low Grade ◽  
Toll Like Receptors ◽  
Inflammatory Reactions

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. The pathogenesis of this syndrome is not yet fully understood. Previous studies indicate the coexistence of low-grade chronic inflammation and PCOS. Toll-like receptors (TLRs) play a key role in the inflammatory reactions. They induce an innate immune response when in contact with pathogen-associated molecular patterns (PAMP). TLRs expression on several cell types has been described, including immune cells, epithelial and endothelial cells, adipocytes, pancreatic beta-cells and ovarian tissue. The stimulation of TLRs triggers signaling pathways, which in turn leads to proinflammatory cytokines production, including IL-6 and TNF alpha. Elevated concentrations of these cytokines were also observed in patients with PCOS. Currently, there are few studies about the role of TLRs in the pathogenesis of PCOS. Women with this syndrome are more frequently diagnosed with metabolic disorders, such as obesity or insulin resistance (IR). The substances released from adipose tissue, including free fatty acids, contribute to the increased activation of the two TLRs - 2 and 4. Recent data also confirms their overexpression in women with PCOS. Increased activation and the presence of specific gene polymorphisms for TLR2 and TLR4 is presumed to be a contributor to the development of IR and hyperandrogenism in women with PCOS.

Glycoprotein A and B Height-to-Width Ratios as Obesity-Independent Novel Biomarkers of Low-Grade Chronic Inflammation in Women with Polycystic Ovary Syndrome (PCOS)

2019 ◽  
Vol 18 (11) ◽  
pp. 4038-4045 ◽  
Author(s):  
Rocío Fuertes-Martín ◽  
Samuel Moncayo ◽  
Maria Insenser ◽  
M. Ángeles Martínez-García ◽  
Manuel Luque-Ramírez ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Chronic Inflammation ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Novel Biomarkers

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome

2015 ◽  
Vol 33 (04) ◽  
pp. 257-269 ◽  
Author(s):  
Soulmaz Shorakae ◽  
Helena Teede ◽  
Barbora de Courten ◽  
Gavin Lambert ◽  
Jacqueline Boyle ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Low Grade Inflammation

scholarly journals The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty

2021 ◽  
Vol 11 ◽  
Author(s):  
YuShuang Xu ◽  
XiangJie Liu ◽  
XiaoXia Liu ◽  
Di Chen ◽  
MengMeng Wang ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiota ◽  
Chronic Inflammation ◽  
Healthy Aging ◽  
Low Grade ◽  
Age Related ◽  
Composition Structure ◽  
Low Grade Inflammation

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.

scholarly journals Chronic Low Grade Inflammation in Pathogenesis of PCOS

2021 ◽  
Vol 22 (7) ◽  
pp. 3789
Author(s):  
Ewa Rudnicka ◽  
Katarzyna Suchta ◽  
Monika Grymowicz ◽  
Anna Calik-Ksepka ◽  
Katarzyna Smolarczyk ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Polycystic Ovary Syndrome ◽  
Chronic Inflammation ◽  
Polycystic Ovary ◽  
Low Grade ◽  
C Reactive Protein ◽  
Ovary Syndrome ◽  
Gene Markers ◽  
Reactive Protein ◽  
Inflammatory State

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

scholarly journals Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sang-Hyeop Lee ◽  
Nak-Hyeon Choi ◽  
In-Uk Koh ◽  
Bong-Jo Kim ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Positive Role ◽  
Inflammatory Genes ◽  
Altered Gene Expression ◽  
Tnf Α ◽  
Altered Gene ◽  
Geo Database

Abstract Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between (1) lean and obese ACs, (2) lean and obese preACs, (3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-α and IL-1β, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

The role of chronic inflammation and Leu55Met PON1 polymorphism in the pathogenesis of polycystic ovary syndrome

2010 ◽  
Vol 26 (9) ◽  
pp. 673-683 ◽  
Author(s):  
Agnieszka Lenarcik ◽  
BoŻena Bidzińska-Speichert ◽  
Urszula Tworowska-Bardzińska
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Chronic Inflammation ◽  
Polycystic Ovary ◽  
Ovary Syndrome
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