Role of estrogen receptors in health and disease

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 18, 2022

Estrogen receptors (ERs) regulate multiple complex physiological processes in humans. Abnormal ER signaling may result various disorders, including reproductive system-related disorders (endometriosis, and breast, ovarian, prostate cancer), bone-related abnormalities, lung cancer, cardiovascular disease, gastrointestinal urogenital tract neurodegenerative cutaneous melanoma. alpha (ERα), beta (ERβ), novel G-protein-coupled estrogen receptor 1 (GPER1) have been identified as the most prominent ERs. This review provides an overview of ERα, ERβ, GPER1, well their functions health disease. Furthermore, potential clinical applications challenges are discussed.

Language: Английский

---

Intricate Connections between the Microbiota and Endometriosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5644 - 5644

Published: May 26, 2021

Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance altered cell profiles, all which may contribute pathogenesis endometriosis. Over time, this dysregulation can progress into a chronic state inflammation, creating an environment conducive increased adhesion angiogenesis, drive vicious cycle endometriosis onset progression. Recent studies have demonstrated both ability induce changes, antibiotics treat Endometriotic microbiotas been consistently associated with diminished Lactobacillus dominance, well elevated abundance bacterial vaginosis-related bacteria other opportunistic pathogens. Possible explanations for implications dysbiosis include Bacterial Contamination Theory activation, cytokine-impaired estrogen metabolism signaling, aberrant progenitor stem-cell homeostasis. Although preliminary, antibiotic probiotic treatments efficacy treating endometriosis, female (FRT) sampling has successfully predicted disease risk stage. Future research should aim characterize “core” upper FRT elucidate mechanisms behind relationship between

Language: Английский

---

Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†

Biology of Reproduction, Journal Year: 2021, Volume and Issue: 105(1), P. 7 - 31

Published: March 19, 2021

Emerging evidence supports the notion that inflammation fosters development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, growth transcription factors have indisputable roles in establishment maintenance disorders by initiating complex cascades promote proliferation, angiogenesis, lesion progression. The interaction between is orchestrated a plethora factors, sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk diet, vitamin D, immune system. role these not limited to local pathobiology but also extends involve clinical sequelae range from those confined reproductive tract, such as infertility malignancies, systemic complications cardiovascular disease. Enhanced understanding intricate mechanisms this association will introduce us unvisited pathophysiological perspectives guide future diagnostic therapeutic implications aimed at reducing burden disorders. Utilization inflammatory markers, microRNA, molecular imaging adjuncts may be valuable, noninvasive techniques for prompt detection Further, use novel well previously established therapeutics, immunomodulators, hormonal treatments, medications, cyclooxygenase-2 NF-κB inhibitors, can target pathways involved their pathogenesis. In comprehensive review, we aim dissect existing literature on proposed underlying interactions, its contribution sequelae, entails.

Language: Английский

---

Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% reproductive-aged women a well-recognized cause chronic pelvic pain infertility. Despite still unknown etiology endometriosis, much evidence suggests participation epigenetic mechanisms in disease etiopathogenesis. The main rationale based on fact that heritable phenotype changes do not involve alterations DNA sequence are common triggers for hormonal, immunological, disorders, which play key role formation endometriotic foci. Epigenetic regulating T-cell responses, including methylation posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work concert with organ structural cells generate appropriate immune responses functionally shaped by organ-specific environmental conditions. Thus, failure precisely regulate cell transcription may result compromised immunological integrity an increased risk disorders. coexistence endometriosis autoimmunity well-known occurrence. Recent research results indicate regulatory (Treg) number highly active Tregs macrophages have been found peritoneal fluid from endometriosis. Elimination function imbalance between helper Th1 Th2 types reported endometria endometriosis-associated review aims present state art recognition reprogramming factor pathophysiology context T-cell-related autoimmunity. new potential therapeutic approaches modulation and/or adoptive transfer will also be outlined.

Language: Английский

---

The role of iron in the pathogenesis of endometriosis: a systematic review

Human Reproduction Open, Journal Year: 2023, Volume and Issue: 2023(3)

Published: Jan. 1, 2023

What is the role of iron in pathophysiology endometriosis?Iron excess demonstrated wherever endometriotic tissues are found and associated with oxidative stress, an inflammatory micro-environment, cell damage; iron-mediated stress independently linked to subfertility, symptom severity, malignant transformation.Iron tissues, multiple mechanisms have been studied posited explain this. It clear that plays a vital promoting damage. The evidence base large, but no comprehensive reviews exist summarize our understanding highlight overarching themes further suggest future directions study for field.This systematic review thematic analysis retrieved studies from PubMed, Embase, Web Science, Cochrane Library databases searches were conducted inception through August 2022. Human animal published English language included identified using combination exploded MeSH terms ('Iron' 'Endometriosis') free-text search ('Iron', 'Ferric', 'Ferrous', 'Endometriosis', 'Endometrioma').This was reported accordance PRISMA guidelines. All reporting original data concerning or complexes endometriosis included. Studies did not report provided field excluded. Bias completed each by Newcastle-Ottawa scoring system.There 776 records these screened down 53 which met eligibility criteria, including 6 47 human studies, 3556 individual participants. Iron various fluids, ovarian endometriomas, follicles, ectopic lesions, peritoneal fluid. Markers strongly high levels, aberrant expression iron-transport proteins has demonstrated. Abnormal resistance ferroptosis likely. Iron-mediated responsible pro-inflammatory micro-environment and, possibly, transformation.A minority objectively low quality risk bias may lead misleading conclusions. Additionally, failed appropriately characterize patients known confounding variables, such as menstrual cycle phase, introduce findings.Current literature depicts central mechanics subsequent endometriosis. likely at least partly persistence proliferation lesions. As such, represent attractive target novel therapeutics, chelators effectors iron-oxidative pathway. There significant gaps current understanding, this highlights recommends several topics research. These include chelation, ferroptosis, relationship between localized hypoxia, systemic endometriosis, transformation.J.W. S.G.P. supported clinical fellowships Liverpool University Hospital NHS Foundation trust. No additional funding requested required completion work. C.J.H. Wellbeing Women project grant (RG2137). D.K.H. (RG2137) MRC research training fellowship (MR/V007238/1). authors conflicts interest declare.A protocol prospectively registered PROSPERO database 2021 (CRD42021272818).

Language: Английский

---

Endometriosis Treatment: Role of Natural Polyphenols as Anti-Inflammatory Agents

Nutrients, Journal Year: 2023, Volume and Issue: 15(13), P. 2967 - 2967

Published: June 30, 2023

Endometriosis is an estrogen-dependent common chronic inflammatory disease defined by the presence of extrauterine endometrial tissue that promotes pelvic pain and fertility impairment. Its etiology complex multifactorial, several not completely understood theories have been proposed to describe its pathogenesis. Indeed, this affects women’s quality life their reproductive system. Conventional therapies for endometriosis treatment primarily focus on surgical resection, lowering systemic levels estrogen, with non-steroidal anti-inflammatory drugs counteract response. However, although these strategies shown be effective, they also show considerable side effects. Therefore, there a growing interest in use herbal medicine endometriosis; however, date, only very limited literature present topic. Polyphenols display important anti-endometriotic properties; particular, are potent phytoestrogens parallel modulates estrogen activity exerts activity. The aim review provide overview polyphenols endometriosis.

Language: Английский

---

Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101250 - 101250

Published: Oct. 30, 2023

In clinical practice, the co-existence of endometriosis and gastrointestinal symptoms is often observed. Using large-scale datasets, we report a genetic correlation between irritable bowel syndrome (IBS), peptic ulcer disease (PUD), gastro-esophageal reflux (GORD), combined GORD/PUD medicated (GPM) phenotype. Mendelian randomization analyses support causal relationship predisposition to IBS GPM. Identification shared risk loci highlights biological pathways that may contribute pathogenesis both diseases, including estrogen regulation inflammation, potential therapeutic drug targets (CCKBR; PDE4B). Higher use IBS, GORD, PUD medications in women with higher hormone therapies PUD, co-occurrence these conditions highlight for repositioning contraindications. Our results provide evidence etiology have important implications diagnostic treatment decisions diseases.

Language: Английский

---

Pathogenesis of Endometriosis and Endometriosis-Associated Cancers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7624 - 7624

Published: July 11, 2024

Endometriosis is a hormone-dependent, chronic inflammatory condition that affects 5-10% of reproductive-aged women. It complex disorder characterized by the growth endometrial-like tissue outside uterus, which can cause pelvic pain and infertility. Despite its prevalence, underlying molecular mechanisms this disease remain poorly understood. Current treatment options are limited focus mainly on suppressing lesion activity rather than eliminating it entirely. Although endometriosis generally considered benign condition, substantial evidence suggests increases risk developing specific subtypes ovarian cancer. The discovery cancer driver mutations in endometriotic lesions indicates may share pathways with Moreover, application single-cell spatial genomics, along development organoid models, has started to illuminate etiology. This review aims summarize key genetic alterations drive progression malignancy. We also significant recent advances understanding basis disorder, as well novel approaches vitro models offer new avenues for improving our pathology targeted therapies.

Language: Английский

---

The Known, the Unknown and the Future of the Pathophysiology of Endometriosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5815 - 5815

Published: May 27, 2024

Endometriosis is one of the most common causes chronic pelvic pain and infertility, affecting 10% women reproductive age. A delay up to 9 years estimated between onset symptoms diagnosis endometriosis. currently defined as presence endometrial epithelial stromal cells at ectopic sites; however, advances in research on endometriosis have some authors believing that should be re-defined “a fibrotic condition which stroma epithelium can identified”. There are several theories etiology disease, but origin remains unclear. This review addresses role microRNAs (miRNAs), naturally occurring post-transcriptional regulatory molecules, endometriotic lesion development, inflammatory environment within peritoneal cavity, including cytokines play during development how animal models helped our understanding pathology this enigmatic disease.

Language: Английский

---

The Impact of Endometriosis on Pregnancy

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(1), P. 126 - 126

Published: Jan. 22, 2024

Despite the increased frequency of endometriosis, it remains one most enigmatic disorders regarding its effects on pregnancy. Endometriosis adversely affects both natural and assisted conception. Impaired folliculogenesis, which causes follicular dysfunction low egg quality, as well luteal phase problems, reduced fertilization, abnormal embryogenesis, are some mechanisms advocated to explain reproductive dysfunction. There is a rising need for comprehensive study potential negative consequences this condition pregnancy outcomes, including postpartum period, more women with medical history endometriosis become pregnant. Obstetrical complications (small gestational age [SGA], cesarean section [CS], miscarriage, hemorrhage, placental adhesion, preterm delivery) statistically elevated in endometriosis. Furthermore, ruptured ovarian endometrioma, appendicitis, intestinal perforation, hemoperitoneum have been described Obstetricians largely unfamiliar these complications, they not thoroughly investigated. The development pathogenesis an important field has yet fully elucidated. Finding crucial new effective strategies treat condition. can impact obstetric neonatal outcomes pregnancy, addition To date, no additional monitoring recommended pregnancies However, studies urgently needed assess tailored

Language: Английский

---