Serum Markers for the Noninvasive Diagnosis of Endometriosis

Luisi, Stefano; Pinzauti, Serena; Regini, Cristina

doi:10.2217/whe.15.46

Cited by 18 publications

(12 citation statements)

References 58 publications

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“…Proteomic approaches have been used to identify possible biomarkers correlating with endometriosis pathology, mostly in serum or PF 2,28,29 . Besides critical cytokines and growth factors such as interleukin IL-1β, IL-6, IL-10 or VEGF, these studies have also identified alterations in indicators of oxidative stress, such as paraoxonase, superoxide dismutase (SOD), thioredoxin binding protein, and others 30 , again lending support to the hypothesis of oxidative stress as a hallmark of disease.…”

mentioning

confidence: 99%

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

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Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.Endometriosis, affecting 5-10% of women in reproductive age, is a gynaecological disease characterized by the presence of ectopic endometrial tissue most often found in the pelvic cavity 1,2 . Retrograde menstruation is a widely accepted pathogenic mechanism for the formation of peritoneal lesions, in which uterine epithelial and stromal cells are disseminated during menstruation and implanted into the peritoneal cavity via the Fallopian tubes 3,4 . Peritoneal lesions are macroscopically classified based on colour, appearing as white, red, brown, or black lesions. This appearance seems to be determined by endometrial gland content and a variable adjacent stromal reaction, likely reflecting a chronicity process rather than different levels of disease activity 5 . Additional contributors to disease such as genetic, epigenetic and environmental factors exist, since a majority (90%) of women undergo retrograde menstruation associated with successful clearance of menstrual debris from the peritoneal cavity 3,6-9 . However, the formation of ectopic endometrial lesions is a signature event that leads to the hallmarks of disease, comprising sustained inflammation, severe and chronic pain, as well as subfertility 10,11 . www.nature.com/scientificreports www.nature.com/scientificreports/ proteomic and transcriptomic arms of the study distinct patient populations were used and further collection details are provided in the SI material.Protein extraction and sample preparation. Tissue material was homogenised and extracted, protein extracts were subjected to in-solution trypsin digestion and data processed as described 51 . Transcriptome analysis. Illumina compatible next-generation sequencing libraries were prepared and sequenced from ribosomal RNA depleted or...

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mentioning

confidence: 99%

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

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“…This is a behavioral parameter that has not been replicated from the clinical scenario because women with endometriosis tend to show a higher incidence of introversion anxiety. 48 This indicates that the behavioral tests used in this study might not be sensitive enough to measure certain aspects of anxiety that can be present in the animal, since our previous work has demonstrated that administered external stress can produce increased anxiety as assessed by increased fecal pellet counts. 11 Our data parallel the clinical observations found in women with endometriosis, 13,14 showing a decrease in cortisol basal state, even when controlling for treatment status of the patients.…”

Section: Discussionmentioning

confidence: 91%

Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression

et al. 2018

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Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger area enclosure) or no enrichment (endo-NE: 2 rats per cage) starting on postnatal day 21. After 8 weeks, sham surgery or surgical endometriosis was induced by suturing uterine horn tissue next to the intestinal mesentery, then allowed to progress for 60 days during which EE or NE continued. At the time of killing, we measured anxiety behaviors, collected endometriotic vesicles and uterus, and processed for quantitative real-time polymerase chain reaction for corticotropin-releasing hormone (CRH), urocortin-1, CRH receptors type 1 and type 2, and glucocorticoid receptor (GR). Endometriosis did not affect anxiety-like behaviors, yet rats in enriched conditions showed lower basal anxiety behaviors than the nonenriched group. Importantly, the endo-EE group showed a 28% reduction in the number of endometriosis vesicles and the vesicles were significantly smaller compared to the endo-NE group. Endometriosis increased CRH and GR only in the vesicles of endo-NE, and this increase was dampened in the endo-EE. However, urocortin 1 was increased in the vesicles of the endo-EE group, suggesting different pathways of activation of CRH receptors in this group. Our results suggest that the use of multimodal complementary therapies that reduce stress in endometriosis could be an effective and safe treatment alternative, with minimal side effects.

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“…Additionally, elevated monocyte chemotactic protein-1 (MCP-1) values were observed in peritoneal fluid and plasma in women with endometriosis, especially in the early stages of the disease. Another study revealed its elevated values in the more advanced stages [8].…”

Section: Immunological Markersmentioning

confidence: 94%

“…It is considered that the development of non-invasive diagnostic tests such as 'biomarkers' would have a clear impact in reducing diagnosis time and monitoring the progress of the disease and the effectiveness of treatment [5]. To replace invasive diagnostic methods, biomarkers could be considering clinically useful if they comply with predetermined criteria -sensitivity 94% and specificity 79% [8,9]. This paper aims to describe and discuss the current status of biomarkers of endometriosis in serum.…”

Section: Introductionmentioning

confidence: 99%

Novel Diagnostic Markers for Endometriosis

Kimber-Trojnar¹,

Pilszyk²,

Niebrzydowska³

et al. 2021

Preprint

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Endometriosis is a disease that affects women of reproductive age and has a significant impact on their well-being. The main symptoms are dysmenorrhea, chronic pelvic pain and infertility. The diagnostic process in many cases is very long and can take up to 8-12 years. Laparoscopy, which is an invasive method, is still necessary to confirm final identification. Therefore, the development of diagnostic markers seems to be crucial for the diagnosis and proper treatment of women affected by endometriosis as soon as possible. Still the most frequently studied and used marker is Cancer Antigen 125 (CA-125). Other glycoproteins, growth factors and immune markers seem to play an important role. However, the search for the ideal endometriosis marker is still ongoing. Developing researches on endometriosis pathogenesis help to identify potential biomarkers or sets of biomarkers in order to improve and speed up the diagnostic process in a non-invasive way.

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Serum Markers for the Noninvasive Diagnosis of Endometriosis

Cited by 18 publications

References 58 publications

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression

Novel Diagnostic Markers for Endometriosis

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