The role of peripheral nerve signaling in endometriosis

Godin, Stephen K.; Wagner, John A.; Huang, Pearl S.; Bree, Dara

doi:10.1096/fba.2021-00063

Cited by 13 publications

(7 citation statements)

References 114 publications

(136 reference statements)

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“…BDNF and NTRK2 were more significantly expressed in the uterus of women with endometriosis compared to disease-free controls (28); BDNF has been found to be dysregulated and overexpressed in ectopic but not in eutopic endometrial tissue. Interestingly, BDNF is a down-stream effector of estrogens mediating the pro-proliferative effects of estrogens promoting nociceptive pain (29,30). Estrogens strongly induce BDNF production by macrophages, and BDNF promotes neurogenesis through its binding to NTRK2 receptors on nerves.…”

Section: Article Length Targetmentioning

confidence: 99%

Development and Validation of a novelin vitrodiagnostic test for endometriosis

Herranz-Blanco¹,

Daoud²,

Viganò

et al. 2023

Preprint

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Objective: To develop a non-invasive diagnostic test for endometriosis. Design: We conducted two studies: the development study (study 1) aimed at (i) evaluating the ability of CA125, brain-derived neurotrophic factor (BDNF) and clinical variables in segregating between cases and controls and (ii) developing a diagnostic algorithm based on those results. In the validation study (study 2), the clinical performance of the developed in vitro diagnostic (IVD) test, in diagnosing endometriosis was validated. Interventions: Serum samples and clinical variables extracted from psychometric questionnaires were collected from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of endometrial glands and/or stroma in the excised lesions. Main outcome measures: Study 1 and 2 included n=204 and n=79 patients, respectively. CA125 and BDNF concentrations were determined using the endometriosis IVD ELISA kit. In study 2, serum CA125 and BDNF concentrations and clinical variables were introduced into the IVD test software hosting the data treatment algorithm, which generates the qualitative diagnostic result (positive or negative). Results: Results from study 1 showed that, for both biomarkers levels, a statistically significant difference was found between cases and controls. Among all clinical variables related to patients medical history considered, six were significantly different between cases and controls: record of a previous surgery to investigate endometriosis presence, painful periods leading to referral for endometriosis presence, severity of menstrual pain during last cycle, age at first experience of intercourse pain, age at first regular use of painkillers and age at first diagnosis of ovarian cyst. In study 2, the novel endometriosis IVD test demonstrated sensitivity and specificity values of 46.2% (25.5-66.8%) and 100% (86.7-100%), respectively. Conclusion: BDNF and CA125, together with patient clinical variables, allowed efficient segregation between controls and endometriosis cases. Due to its high specificity, the novel endometriosis IVD test is an accurate rule-in non-invasive method, potentially contributing to diagnose endometriosis.

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Section: Article Length Targetmentioning

confidence: 99%

Development and Validation of a novelin vitrodiagnostic test for endometriosis

Herranz-Blanco¹,

Daoud²,

Viganò

et al. 2023

Preprint

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“…This reinforces the association between neural recruitment and aggressiveness of DSIE. Neural recruitment is believed to be regulated by several neurotrophic factors and neuroimmune interactions 103 . (Figure 2).…”

Section: Biological Behaviour Of Dsie and Its Molecular Mechanismsmentioning

confidence: 99%

Digestive system deep infiltrating endometriosis: What do we know

Yin,

Li,

Liu

et al. 2023

J Cellular Molecular Medi

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Digestive system infiltrating endometriosis (DSIE) is an uncommon form of endometriosis in the digestive system. DSIE often occurs in the intestines (especially the sigmoid rectum), liver, gallbladder and pancreas. Clinically, DSIE presents with the same symptoms as endometriosis, including cyclic pain, bleeding and infertility, in addition to specific biliary/intestinal obstruction and gastrointestinal bleeding. Compared to general endometriosis, DSIE has unique biological behaviour and pathophysiological mechanisms. Most DSIEs are deep invasive endometrioses, characterized by metastasis to the lymph nodes and lymphatic vessels, angiogenesis, peripheral nerve recruitment, fibrosis and invasion of surrounding tissues. DSIE‐related peripheral angiogenesis is divided into three patterns: angiogenesis, vasculogenesis and inosculation. These patterns are regulated by interactions between multiple hypoxia‐hormone cytokines. The nerve growth factors regulate the extensive neurofibril recruitment in DSIE lesions, which accounts for severe symptoms of deep pain. They are also associated with fibrosis and the aggressiveness of DSIE. Cyclic changes in DSIE lesions, recurrent inflammation and oxidative stress promote repeated tissue injury and repair (ReTIAR) mechanisms in the lesions, accelerating fibril formation and cancer‐related mutations. Similar to malignant tumours, DSIE can also exhibit aggressiveness derived from collective cell migration mediated by E‐cadherin and N‐cadherin. This often makes DSIE misdiagnosed as a malignant tumour of the digestive system in clinical practice. In addition to surgery, novel treatments are urgently required to effectively eradicate this lesion.

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“…Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, these data suggest that the chronic inflammatory condition in EM might contribute to the increase of semaphorins, which could affect the innervation in peritoneal EM [ 53 , 54 ].…”

Section: Neuroimmunomodulation In Endometriosismentioning

confidence: 99%

Neurogenic Inflammation in the Context of Endometriosis—What Do We Know?

Velho

Taube

Sehouli

et al. 2021

IJMS

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Endometriosis (EM) is an estrogen-dependent disease characterized by the presence of epithelial, stromal, and smooth muscle cells outside the uterine cavity. It is a chronic and debilitating condition affecting ~10% of women. EM is characterized by infertility and pain, such as dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Although EM was first described in 1860, its aetiology and pathogenesis remain uncertain. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with EM but also contribute to a growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. Here we review the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the role of this system, as well as its interactions with immune cells, will unearth novel disease-relevant pathways and targets, providing new therapeutics and better-tailored treatment options.

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The role of peripheral nerve signaling in endometriosis

Cited by 13 publications

References 114 publications

Development and Validation of a novelin vitrodiagnostic test for endometriosis

Development and Validation of a novelin vitrodiagnostic test for endometriosis

Digestive system deep infiltrating endometriosis: What do we know

Neurogenic Inflammation in the Context of Endometriosis—What Do We Know?

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