Estrogen-dependent Disease Research Articles

Designing and validating an adaptation tool for endometriosis: an exploratory mixed method study protocol

BackgroundEndometriosis is a benign and chronic gynecological estrogen-dependent condition. Research findings have highlighted its impact on different aspects of women's lives. Enhancing quality of life and supporting the well-being of those affected is advised. Yet, none of the conducted studies have taken action toward these objectives. Therefore, the present study will be conducted with the aim of "Designing adaptation tool for endometriosis".Methods/designThe method used in this study is an exploratory mixed-method study. The study will consist of two phases, starting with a qualitative phase followed by a quantitative phase. Upon approval Ethics Code from the endometriosis clinic at Imam Reza Hospital in Mashhad, Iran. The research will involve women of reproductive age diagnosed with endometriosis. In-depth and semi-structured interviews with open-ended questions will be conducted. The research aims to explore the experiences of women with endometriosis in adapting to the condition, utilizing qualitative content analysis with an approach based on the "ROY adaptation model." Sampling will be purposive until data saturation is achieved. Data analysis will follow the suggested steps using Elo Kingas' method and MAXQDA20 software. Tool design will involve an inductive approach (informed by qualitative findings) and a comparative method (based on literature review) to develop and refine tool items.DiscussionThis study is the first to employ a mixed-method approach in developing an adaptation tool for endometriosis. It uncovers underlying issues in the attitudes of patients, medical staff, and healthcare providers, offering insight into factors that can enhance the health and quality of life of affected women. The research findings can inform the creation of a relevant strategy for policymakers, planners, and healthcare professionals to better address the needs of women impacted by endometriosis.Ethical code: IR.MUMS.NURSE.REC.1403.069.

Ovarian Endometrioma Disrupts Oocyte-Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects.

Ovarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen-dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, particularly through its direct impact on oocyte-cumulus cell (CC) communication and related pathways, remain poorly understood. This study investigates the impact of OEM on oocyte-CC communication and explores melatonin's therapeutic potential. We used a mouse model of OEM and employed ovarian transcriptome and gene set enrichment analyses to identify disrupted gene pathways, alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis for intercellular communication, and mitochondrial function assessments for cellular metabolism. Our results showed that OEM significantly impairs steroidogenesis and cumulus cell function, leading to increased apoptosis, disrupted transzonal projections (TZPs), and impaired antioxidant transfer to oocytes. This culminates in oxidative stress, mitochondrial dysfunction, and compromised ATP production. OEM oocytes also exhibited severe abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, and increased aneuploidy. This study identifies disrupted TZPs as a key pathological feature in OEM and highlights melatonin's potential to restore intercellular communication, mitigate oxidative damage, and improve reproductive outcomes.

Novel screening approach for stem cell selective inhibitors and their possible translational therapeutic potential for endometriosis.

Endometriosis is an estrogen-dependent benign disease characterized by growth of the endometrial tissue outside the uterine wall. Several reports suggest the possibility of the pathogenesis and recurrence of endometriosis being related to functions of stem/progenitor cells of the endometrium. The drawback of the widely used method of using Hoechst 33342, a fluorescent dye, to collect stem cell-like populations, is the requirement of an ultraviolet (UV) excitation source not commonly provided on standard flow cytometers. Here, we aimed to overcome this hurdle by establishing a novel method that uses DyeCycle Green (DCG), a cell-permeable DNA dye, for collecting a significantly higher fraction of stem cell-like side population (SP) from HHUA cells (human endometrial cancer cell line) with standard equipment without a UV laser. Furthermore, subculturing the DCG-SP cells expanded their population remarkably. The DCG-SP cells possessed stem cell-like characteristics with high expression of stem cell markers such as aldehyde dehydrogenase 1 A (ALDH1A), sushi domain containing 2 (SUSD2), increased colony formation ability, and high tumorigenicity in vivo, although the expression of some stem cell markers varied during expansion. We screened inhibitors for selective proliferation of the DCG-SP cells over immortalized endometrial cells (EM-E6/E7/hTERT-2 cells) and identified two effective compounds disulfiram and NSC319726. In addition, these compounds inhibited the colony formation and invasiveness of the DCG-SP cells. Our DCG-mediated screening of SP cells would possibly be translational to identify compounds that selectively target stem cells for the treatment and inhibition of recurrence of endometriosis.

Quantification of Free Circulating DNA and Differential Methylation Profiling of Selected Genes as Novel Non-Invasive Biomarkers for Endometriosis Diagnosis.

Endometriosis is a chronic, estrogen-dependent disorder associated with the presence of endometrial cells mainly in the pelvic cavity, causing systemic immune inflammation, infertility, epigenetic dysregulation of differential DNA methylation, coelomic metaplasia, and pain. It affects approximately 10-12% of women. Despite decades of research, full pathophysiology, a diagnostic roadmap, and clinical management strategies for endometriosis are not yet fully elucidated. Cell-free DNA (Cf-DNA) in the peripheral blood of diseased and healthy individuals was discovered in the 1950s. Quantifying peripheral Cf-DNA and the specific differential methylation of a group of genes have been proposed as potential non-invasive diagnostic biomarkers for somatic and constitutional genetics and for various other pathological disorders. In this study, we investigated the Cf-DNA levels of 78 young women, 38 of whom had endometriosis confirmed via laparoscopy and 40 of whom were healthy. We found a significant difference between the two groups when Cf-DNA was quantified, with 3.9 times more Cf-DNA in the serum of women with endometriosis. We also identified nine target genes potentially involved in the pathogenesis of endometriosis, with a different methylation profile between the two groups. Our data suggest that the combination of cell-free DNA quantification and the assessment of the epigenetic signature of differential methylation of nine genes can be proposed as a non-invasive predictive and diagnostic test for endometriosis.

FOXL2 Knockdown Inhibits the Progression of Endometriosis.

Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs). FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2'-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry. The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs. FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.

Thoracic Endometriosis Syndrome: A Comprehensive Review and Multidisciplinary Approach to Management.

Background: Endometriosis is a systemic, inflammatory, estrogen-dependent condition characterized by endometrial stroma and gland-like lesions outside of the uterus. It causes a range of symptoms, notably chronic pelvic pain, infertility and organ dysfunction. Thoracic endometriosis syndrome (TES) has been described as endometriosis that is found in the lung parenchyma, pleura and diaphragm. It may be asymptomatic or present with symptoms of catamenial pneumothorax, hemothorax, hemoptysis, isolated chest pain, shoulder pain or findings of lung nodules. Aim: The aim of this review is to provide a comprehensive overview of thoracic endometriosis syndrome (TES), including its clinical presentation, diagnostic challenges, and current management strategies. This review aims to highlight the importance of a multidisciplinary approach in the treatment of TES, emphasizing conservative management and the role of minimally invasive surgical techniques for refractory cases. Conclusions: Thoracic endometriosis syndrome appears to be a marker of severe endometriosis. As much as possible, the patient with TES is managed conservatively, with surgery reserved for refractory cases. When surgery is recommended, the procedure is conducted through a multidisciplinary minimally invasive approach, with video-assisted thoracoscopic surgery (VATS) and video-assisted laparoscopy. Meticulous intraoperative survey, the removal of endometriosis implants with and without robotic assistance and post-operative hormonal therapy may be recommended to prevent recurrence.

AURKA inhibits the decidualization of the eutopic endometrium in endometriosis through NF-κB p65†.

Endometriosis is an estrogen dependent disease, which is related to infertility. Decidualization is a prerequisite for successful implantation of human embryos, and endometriosis affects the occurrence of decidualization. However, the mechanism that affects decidualization in endometriosis is not fully understood. Here, we find that Aurora kinase A (AURKA) is upregulated in the eutopic endometrium of endometriosis. AURKA inhibits the decidualization of stromal cells in the eutopic endometrium of endometriosis. Furthermore, in animal experiments, AURKA promotes endometriosis and inhibits decidualization in mice with endometriosis, leading to decreased expression of decidualization markers, such as prolactin (PRL), insulin-like growth factor-binding protein-1 (IGFBP1) and desmin. Afterwards, we find that nuclear factor-κB (NF-κB) p65 is a new substrate of AURKA. AURKA interaced with p65 to promoted its phosphorylation and nuclear translocation. Meanwhile, AURKA enhances the protein stability of p65 by prolonging its half-life. In summary, AURKA inhibits the decidualization of the eutopic endometrium in patients with endometriosis by regulating p65, which may provide new ideas for improving decidualization defect in patients with endometriosis.

Combine Surgery and In Vitro Fertilization (IVF) in Endometriosis-Related Infertility: When and Why.

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial tissue outside the uterus, causing pelvic pain and infertility. Infertility arises mainly due to inflammatory mediators in the peritoneal fluid, contributing to local hypoestrogenism, which appears to exacerbate chronic inflammation and sensitize pelvic nerves. Local hypoestrogenism within endometriotic lesions contrasts with the systemic estrogen-dependent nature of the disease. This localized reduction in estrogen levels, resulting from an altered hormonal response, can contribute to the altered immune response and inflammation characteristic of endometriosis, potentially exacerbating tissue damage, promoting fibrosis, adhesions, and endometrioma formation that distort pelvic anatomy, and affecting fertility. Chronic pelvic pain and dyspareunia further complicate conception in affected women. In vitro fertilization (IVF) and laparoscopic surgical excision of endometriotic lesions are the two primary management options for endometriosis-related infertility, although current data provide limited guidance on when to prefer one approach over the other. It is generally accepted that treatment strategies must be individualized according to the patient's wishes, symptomatology, age and the preferences of the woman and the couple. Timely intervention and structured follow-up for symptomatic women wishing to conceive may maximize conception rates within two years post-surgery, while minimizing the need for repeated interventions, which should be avoided. On the other hand, first-line IVF is particularly viable in cases of unoperated deep infiltrating endometriosis in asymptomatic women, or for those ineligible for or opposed to surgery. This review aims to evaluate the most recent data on endometriosis-related infertility to identify evidence-based key points that can enhance tailored management in clinical practice.

A cross-sectional study on the relationship between dietary fiber and endometriosis risk based on NHANES 1999–2006

Endometriosis is a chronic inflammatory disease and an estrogen-dependent disease, so dietary factors that can modulate estrogen activity may be clinically important. Dietary fiber, widely distributed in vegetables and fruits, is closely associated with a plant-based diet. Therefore, this study aims to analyze and explore the relationship between dietary fiber intake and the risk of endometriosis providing insights for future clinical significance and treatment approaches. This cross-sectional study obtained data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 for women aged 20–54 years. A total of 2840 subjects were finally included for analysis, 2599 (91.51%) in the non-endometriosis group and 241 (8.49%) in the endometriosis group. The study used dietary fibre intake as exposure variable and endometriosis risk as outcome variable. Through the use of multiple regression modelling, subgroup analyses, smoothed curve fitting, and threshold effect tests, we uncovered a significant link between exposure and outcome. In Model 2 (Multiple regression equation model after adjusting all confounding variables), after adjusting for confounders, dietary fiber intake was negatively associated with the likelihood of developing endometriosis(OR = 0.588, 95% CI = 0.360–0.959, p = 0.041). In subgroup analyses stratified by age, race, BMI, educational level, hypertension, diabetes,and hyperlipidemia, significant interactions were visualised from smoothed fitted curves. In the cross-sectional study, a connection was observed between a higher intake of dietary fiber and a decreased risk of endometriosis.

Endometriosis, a novel treatment ahead?

Endometriosis is an estrogen-dependent condition that can lead to significant morbidity, including chronic pelvic pain, multiple surgeries, and infertility. Recent discoveries regarding its genetics, the potential influence of environmental factors and the immune system, along with intrinsic abnormalities in the endometrium of affected women and the secretions from endometriotic lesions, have provided new insights into the disease's pathogenesis. These findings form the basis for developing new treatments aimed at managing disease-related pain and infertility. It was possible to observe a case of remission of symptoms and complete disappearance of lesions on ultrasound images after anthroposophic treatment. Certainly, more cases need to be followed up in the long term to verify whether there has been a real cure for the disease. Case: Brazilian woman in the reproductive period with endometriosis presented remission of symptoms with disappearance of the lesions after anthroposophic treatment

6816 The Estrogen Environment Characteristic of Endometriotic Lesion May Attenuate the Receptor γ-Mediated Antiproliferative Activity of Retinoids

Abstract Disclosure: M. Izawa: None. Y. Azuma: None. F. Taniguchi: None. Background: Endometriosis has been accepted as an estrogen-dependent disease, and the estrogen environment in endometriotic lesions has been proposed as a major background of the pathophysiology. Although the hormonal therapy targeting the reduction of estrogen has been employed to reduce endometriosis-associated symptoms, the limitation of therapy has been well recognized. How to overcome the limitation remains an urgent subject to be explored. [Objective:]We focused on retinoids, which have been known to induce an antiproliferative activity in tumors. Based on the retinoic acid receptor (RAR) expression profile in endometriotic lesions, we evaluated the antiproliferative activity of retinoids using endometriotic cells. Finally, we examined the effect of estrogen on antiproliferative activity. Methods: Endometriotic tissue and cells: Institutional Review Boards approved this project. The chocolate cyst lining in the ovaries of patients with endometriosis was the source of endometriotic tissue. Stromal cells collected from endometriotic tissues were used as endometriotic cells. RAR expression: RNAs were prepared from endometriotic tissues and cells, and single-stranded cDNAs were subjected to RT-PCR. Primers were designed using the UCSF genome browser. Protein expression was examined by Western blotting. Cell proliferation assay: Cells were treated with all-trans retinoic acid (ATRA), selective RAR modulators (sRARMs), BMS753, CD2314 and CD437, RARγ antagonist MM11253 and 17β-estradiol (E2). Viable cells were estimated using WST-8 assay. RNA-seq analysis: Cells were treated with retinoids and E2. RNA samples were used for polyA+ selected library and the strand-specific RNA-seq. Differentially expressed genes with p-values < 0.05 and log2 fold changes > 1 were extracted as responsive genes. Results: RAR expression: Transcripts of wild-type RARα, RARβ, and RARγ were demonstrated in arbitrary 10 regions of patient tissue, and in endometriotic cells. The expression of these RARs was almost at a comparable level. Effect of retinoids and/or estrogen on cell proliferation: Cell proliferation rate was significantly decreased in the presence of ATRA. Among sRARMs tested, only CD437 reduced the cell proliferation. The antiproliferative activity of ATRA was attenuated either in the presence of MM11253 or E2, respectively. ATRA- and/or E2-responsive gene expressions To explore gene expressions in response to retinoids and E2, RNA-seq analysis was performed. The results suggest the diversity of ATRA- and E2-responsive genes in endometriotic lesions.[Conclusion:]Endometriotic cell proliferation was significantly suppressed in response to retinoids through RARγ. The observation that the antiproliferative activity was attenuated in the presence of E2 suggests a suppressive environment against the activity of retinois in endometriotic legions. Presentation: 6/2/2024

Endometriotic lesions and their recurrence: A Study on the mediators of immunoregulatory (TGF-β/miR-20a) and stemness (NANOG/miR-145)

Endometriosis is a common estrogen-dependent disease that involves various cellular processes. Additionally, miRNAs play a crucial role in the development of the disease as an important component of the microenvironment. In this study, tissue specimens of eutopic and ectopic lesions of 20 women, whose endometriosis was later approved by the pathology laboratory, were biopsied through laparoscopy. As a control group, endometrial tissue specimens were collected from 20 women who underwent curettage for reasons unrelated to endometriosis. The expression levels of miR-20A and miR-145 and their target genes, TGF-β and NANOG, were measured in these samples as markers of stemness and immunomodulatory properties, respectively. The study also aimed to compare the expression levels of target genes and miRNAs in ectopic lesions regarding endometriosis recurrence post-surgery. The study revealed that the expression of TGF-β and NANOG genes was significantly upregulated in endometriotic tissues compared to the control group. There was also a notable increase in miR-20A and miR-145 expression in the endometriotic tissues compared to the control group. While there was no significant correlation between the expression of miR-20a and TGF-β, we observed a negative correlation between the expression level of miR-145 and NANOG. Additionally, the ROC curve analysis emphasized miR-14 as a potential biomarker for endometriosis over miR-20a. However, our findings on disease recurrence underscore the importance of miR-20a in the early detection of endometriosis recurrence.

Effects, Doses, and Applicability of Gestrinone in Estrogen-Dependent Conditions and Post-Menopausal Women.

Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims to reevaluate the routes, doses, and applicability proposed for using gestrinone, including its use in new conditions such as menopause, lipedema, and sarcopenia. Here, we present the possible application of gestrinone as a long-acting therapeutic possibility through hormonal implants and the benefits and potential risks. Available evidence on the safety of doses and routes is limited. Gestrinone appears to be effective compared to other progestins and may have some advantages in the treatment of estrogen-dependent pathologies. Future research must evaluate gestrinone's long-term safety and potential therapeutic indications.

Endometriosis: Classification, Risk factors, Diagnosis and management - Review of Literature

Endometriosis is an oestrogen-dependent disease characterised by the presence of the endometrial tissue outside its normal location. Three types of endometriosis are distinguished: ovarian, peritoneal, and deeply infiltrating [1,2].The literature reports that 6-15% of the general female population suffers from endometriosis. This disease occurs mainly in women of reproductive age, but also in young women and postmenopausal women [3]. Symptoms of endometriosis include periodic pain that becomes constant, very painful menstruation, painful intercourse, as well as painful micturition or defecation. Endometriosis is present in up to 35-50% of women diagnosed with infertility. In diagnosing endometriosis, laparoscopy is of utmost importance, as it allows for simultaneous treatment of the condition. Laparoscopy should be preceded by a thorough medical history and imaging diagnostics such as ultrasound or magnetic resonance imaging (MRI).The treatment of endometriosis is divided into pharmacological and surgical methods, which can be either conservative or radical. The type of treatment used depends on the patient's age and reproductive desires, the symptoms present, and the form of the disease. A proper diet and lifestyle play a significant role in the treatment of endometriosis.

Endometriotic lesions express microRNAs that potentially regulate the transcription of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2): a pilot study

ObjectiveEndometriosis is an estrogen-dependent disease. A theory of deficient HSD17B2 activity in endometriotic lesions leading to high local levels of estradiol has been described as a potential molecular mechanism for the disease progression. However, HSD17B2 mRNA is normally expressed in endometriotic tissue, leading us to question whether an excess of microRNAS (miRNAs) could be involved in post-transcriptional silencing of HSD17B2. MethodsThis was a prospective, cross-sectional, pilot study. The study included seven samples of superficial peritoneal endometriosis and 22 samples of eutopic endometrium from 22 reproductive-aged patients submitted to laparoscopy for symptomatic endometriosis. We searched in an experimentally validated microRNA-target interaction online database (miRTarBase) for miRNAs that target the HSD17B2 gene and performed RT-PCR to evaluate their expression in endometriotic lesions and eutopic endometrium. ResultsWe found two miRNAs on the miRTarBase search that interact with HSD17B2: miR-124-3p and miR-26b-5p. RT-PCR analysis showed that both miRNAs were expressed in ectopic tissues as well as in eutopic endometrium. Quantitatively, no significant difference existed between the two tissue groups in either miR-26b-5p (p = 0.08) or miR-124-3p (p = 0.09) expression levels, although the observed trend was towards lower levels of both miRNAs in the endometriotic lesions. ConclusionsThe expression of miRNAs miR-26b-5p and miR-124-3p is not increased in peritoneal endometriosis compared to eutopic endometrium. The regulation of HSD17B2 expression may be more complex than assumed, and it must be further investigated in different clinical scenarios.

CCL18 promotes endometriosis by increasing endometrial cell migration and neuroangiogenesis.

Endometriosis is an estrogen-dependent inflammatory gynecological disease whose pathogenesis is unclear. C-C motif chemokine ligand 18 (CCL18), a chemokine, is involved in several inflammatory diseases. In this study, we aimed to investigate the role of CCL18 in endometriosis and its underlying mechanisms. Human endometrium and peritoneal fluid were obtained from women with and without endometriosis for molecular studies. The expression level of CCL18 in each tissue sample was examined by RNA sequencing analysis, quantitative PCR analysis and immunohistochemistry staining. The effects of CCL18 on cell migration, tube formation and neurite growth were investigated in vitro using primary endometrial cells, human umbilical vein endothelial cells (HUVECs) and dorsal root ganglion (DRG) neurons, respectively. Moreover, the development of endometriosis in mice was studied in vivo by blocking CCL18. CCL18 was shown to be overexpressed in endometrial foci and peritoneal fluid in women with endometriosis and was positively correlated with endometriosis pain. In vitro, CCL18 promoted the migration of ectopic endometrial cells, tube formation of HUVECs, and nerve outgrowth of DRG neurons. More importantly, inhibition of CCL18 significantly suppressed lesion development, angiogenesis, and nerve infiltration in a mouse model of endometriosis. In conclusion, CCL18 may play a role in the progression of endometriosis by increasing endometrial cell migration and promoting neuroangiogenesis.

M1 macrophages as promising agents for cell therapy of endometriosis

Endometriosis is a chronic estrogen-dependent disease characterized by the presence of endometrial glands and stroma outside their normal anatomical location. While laparoscopic removal of foci remains the gold standard therapy, it has limited efficacy and certain risks. However, cell therapy using pro-inflammatory M1 macrophages presents a promising and minimally invasive alternative for treating endometriosis. This approach showcases the potential for innovative and effective treatments for this condition. This study aims to explore the anti-endometriosis properties of M1 macrophages. A reproducible syngeneic mouse model of endometriosis was utilized, revealing that formed foci are primarily composed of macrophages with an anti-inflammatory M2 phenotype rather than M1 macrophages. To investigate further, chemically reprogrammed M1 macrophages were labeled with the membrane fluorescent tag PKH26 and administered to animals with endometriosis. Therapy resulted in a decrease in the number and size of foci, accompanied by a shift in the phenotypic composition of peritoneal macrophages. Specifically, the content of M2 macrophages decreased while that of M1 macrophages increased, resembling the composition of healthy animals. Our study conclusively demonstrates the anti-endometriosis properties of M1 macrophages, providing a strong foundation for future research in the cell therapy of endometriosis.

Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.

Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.

A gluten-free diet for endometriosis patients lacks evidence to recommend it

Endometriosis, an estrogen-dependent chronic disease that is characterized by the presence of endometrium-like tissue outside the uterus, is often associated with symptoms like dysmenorrhea, dysuria, dyschezia, chronic pelvic pain and infertility. Women diagnosed with endometriosis can also report gastro-intestinal symptoms, including bloating, constipation or diarrhea and abdominal cramping, that can be associated with Irritable Bowel Syndrome (IBS) and can result in misdiagnosing endometriosis as IBS at first. Treatment usually involves hormonal therapy, pain management, surgery and/or assisted reproductive techniques in case of infertility. Nonetheless, these treatment methods can be insufficient in alleviating symptoms, or can cause unacceptable side effects leading to non-compliance. Therefore, women often apply self-management strategies including dietary interventions. One of the diets frequently suggested as a tool to manage endometriosis-related symptoms on social media and patient forums, is a gluten-free diet. While a gluten-free diet has been proven effective in managing non-celiac wheat sensitivity or celiac disease, its effectiveness for endometriosis remains uncertain. The Nurses’ Health study II found it unlikely that gluten intake was a strong factor in endometriosis etiology and symptomatology. The most frequently cited and sole published intervention study, to our knowledge, on the efficacy of a gluten-free diet for endometriosis has several important limiting factors, including the absence of a control group. Additionally, gluten consumption is highly susceptible to a placebo- and nocebo effect, where women might experience symptom relief when eliminating gluten, and return of symptoms when they consume gluten again, solely because they believe gluten are bad for them. Despite the inverse association between BMI and endometriosis and between a gluten-free diet and increased BMI, this is an association and no causality was proven. Other factors should be taken into account. Finally, a gluten-free diet is expensive with a limited availability, has a great impact on Quality of Life and without proper dietary guidance may adversely affect the gastro-intestinal microbiome. Therefore, a scientifically substantiated advice regarding the use of a gluten-free diet for endometriosis-related symptoms is currently not available and a gluten-free diet should therefore be discouraged unless there is an additional diagnosis of non-celiac wheat sensitivity or celiac disease.

Experimental Animal Models in Obstetrics and Gynecology

This study focuses on two major diseases affecting women's reproductive health: endometriosis and polycystic ovary syndrome (PCOS). Endometriosis is characterized as an estrogen-dependent condition, highlighting estrogen's role in understanding the disease's development and treatment strategies. Rat and mouse models are crucial for comprehending the pathophysiology of endometriosis and testing new therapeutic approaches. These models are particularly valuable in evaluating the effects of hormones and immune system modulators on endometriosis. Conversely, experimental models of PCOS emphasize the central role of hyperandrogenism in the development of this condition. Models induced by substances like dehydroepiandrosterone, testosterone propionate, and letrozole provide insights into the metabolic and endocrinological disruptions associated with PCOS. The letrozole-induced model, in particular, helps in understanding the relationship between hormonal imbalances and the onset of PCOS. Experimental models of both diseases offer critical knowledge for both basic science research and clinical applications. They provide essential data for understanding the pathophysiology of these conditions and developing new treatment strategies. This study demonstrates how findings from experimental models can improve women's reproductive health and lead to more effective treatments for these diseases. An enhanced understanding of hormonal and immune system mechanisms will guide future research and offer innovative solutions for treating these conditions.