Martínez-Esparza Alvargonzález, María Concepción

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Martínez-Esparza Alvargonzález, María Concepción

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Martínez-Esparza Alvargonzález, María Concepción

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular"B" e Inmunología

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Open Access
Brassica bioactives could ameliorate the chronic inflammatory condition of endometriosis
(MDPI, 2020-12-10) García-Ibañez, Paula; Yepes-Molina, Lucía; Ruiz Alcaraz, Antonio José; Martínez-Esparza Alvargonzález, María Concepción; Moreno, Diego A.; Carvajal, Micaela; García Peñarrubia, María del Pilar; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and sothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
Open Access
Brassica bioactives could ameliorate the chronic inflammatory condition of Endometriosis
(MDPI, ) García Ibánez, Paula; Yepes Molina, Lucía; Moreno, Diego A.; Carvajal, Micaela; García Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are a ected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not e cient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising e ects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women a ected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the e ect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
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Hypothetical roadmap towards endometriosis: prenatal endocrine-disrupting chemical pollutant exposure,anogenital distance,gut-genital microbiota and subclinical infections
(Oxford University Press, 2020-02-28) García Peñarrubia, María del Pilar; Ruiz Alcaraz, Antonio José; Martínez-Esparza Alvargonzález, María Concepción; Marín Sánchez, Pilar; Machado Linde, Francisco; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
BACKGROUND Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. OBJECTIVE AND RATIONALE In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. SEARCH METHODS We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota–immune system interactions. OUTCOMES On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis. WIDER IMPLICATIONS Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.
Open Access
The role of peritoneal macrophages in Endometriosis.
(MDPI, 2021-10-06) Marín Sánchez, Pilar; Machado Linde, Francisco; García Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ramírez Pávez, Tamara Nadira; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology.
Open Access
Systemic immune and tumor marker profiles in ovarian and deep infiltrating endometriosis: associations with disease severity and symptom burden
(MDPI, 2025-10-01) Marín Sánchez, Pilar; Nebot, Ana; García-Izquierdo, Laura; Nieto-Meca, Lucía; Sánchez, Rocío; Machado Linde, Francisco; Martínez-Esparza Alvargonzález, María Concepción; Ramírez Pávez, Tamara Nadira; Bioquímica y Biología Molecular B e Inmunología; Facultad de Medicina
Endometriosis is a chronic, estrogen-dependent inflammatory disease with heterogeneous clinical manifestations and uncertain systemic immune involvement. This study aimed to characterize peripheral immune profiles and circulating tumor markers in women with ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE), and to explore their associations with disease severity, symptom burden, and physical health perception. Peripheral blood leukocyte subsets, plasma cytokines, and tumor markers (CA125, CA19-9, CEA, HE4) were analyzed in 146 patients and 50 healthy controls. OE was associated with increased monocyte counts and reduced neutrophil proportions, while DIE showed elevated levels of IL-8 and Galectin-1. IL-33 levels correlated negatively with the revised American Society for Reproductive Medicine (rASRM) scores and positively with neutrophil proportion, suggesting a role in systemic immune regulation. Tumor marker levels varied by subtype: CA19-9 was higher in OE, and CEA in DIE. CA125 correlated with disease severity, and CEA with monocyte levels. Exploratory heatmaps revealed consistent immune-tumor associations linked to anatomical severity and symptom profiles. Although exploratory, these findings highlight the presence of distinct systemic immune patterns in endometriosis and support the potential of integrative blood-based biomarkers for future diagnostic and stratification strategies.
Open Access
Hypothetical roadmap towards endometriosis: prenatal endocrine- disrupting chemical pollutants exposure, anogenital distance, gut-genital microbiota and subclinical infections.
(Oxford University Press, 2020-02) Marín, Pilar; Machado-Linde, Francisco; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
Background: Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. Objective and rationale: In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Search methods: We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota-immune system interactions. Outcomes: On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis. Wider implications: Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.
Open Access
New potential pharmacological options for endometriosis associated pain
(MDPI, 2024-06-27) García-Izquierdo, Laura; Marín-Sánchez, Pilar; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Bioquímica y Biología Molecular B e Inmunología
Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited ef fectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurpos ing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometri osis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, im proving patients’ overall wellbeing.
Open Access
Optimization of peritoneal fluid and leukocyte collection in patients with endometriosis
(ELSEVIER, 2023-10-04) Machado-Linde, Francisco; García-Peñarrubia, Pilar; Nieto-Meca, Lucía; Marín-Sánchez, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ramírez Pávez, Tamara Nadira; Bioquímica y Biología Molecular B e Inmunología
Objective: To propose a standardized protocol for peritoneal free fluid and leukocyte sample collection in women with endometriosis suitable for biomedical research on the basis of the surgical procedure, the clinical and technical conditions, and the quality of the samples obtained. Design: Video showing the step-by-step collection procedure and the suitability of samples obtained for biomedical research. Subjects: This study included 103 women with confirmed endometriosis by pathology analysis, who signed informed consent and were recruited from the Hospital ‘‘Virgen de la Arrixaca’’, Murcia, Spain. The study was approved by the Ethics Committee of University of Murcia (CEI 3156/2020). Main Outcome Measures: We analyzed the presence of free fluid in the peritoneal cavity and its relationship with hormonal treatment intake. In addition, the presence of blood contamination, the number of viable leukocytes and macrophages in free peritoneal fluid and lavages as well as their relationship with the lavage volume used, the body mass index, and the age of patients were analyzed. Results: The presence of free peritoneal fluid, in which cells and molecules could be quantified, was scarce in the patients (21%), and it was not significantly related to hormonal treatment intake. The cell viability was higher than 98% in all collected samples; although 54% showed good quality and enough cellularity to be used in biomedical research, 40% were contaminated with blood and 6% had low cellularity. The number of leukocytes and macrophages recovered from the peritoneal lavages correlated positively with the lavage volume used and negatively with the body mass index and was independent of the age of the patients. Conclusion: We describe a standardized step-by-step procedure for peritoneal fluid and leukocyte collection in women with endometriosis, suitable for biomedical research, taking into account that not all women present free fluid in the peritoneal cavity. We propose to increase the lavage volume recommended by the World Endometriosis Research Foundation from 10 mL to at least 40 mL of sterile saline solution and its mobilization for at least 30 seconds within the peritoneal cavity, especially in patients with higher body mass index, to improve the efficiency of the procedure.
Restricted
Impact of deep endometriosis with and without ovarian involvement on quality of life compared to exclusive ovarian endometriosis
(Elsevier, 2025-05-10) Marín Sánchez, Pilar; Martínez-Esparza Alvargonzález, María Concepción; García Peñarrubia, María del Pilar; Ruiz Alcaraz, Antonio José; Arense Gonzalo, Julián Jesús; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Objetivo: Estudiar si hay diferencia en la calidad de vida en pacientes que presentan endometriosis profunda con o sin afectación ovárica (DE) frente a pacientes con endometriosis ovárica exclusivamente (OMA). Materiales y método: Se ha diseñado un estudio prospectivo observacional en pacientes que padecen endometriosis diagnosticadas mediante clínica y pruebas de imagen o confirmación histológica mediante laparoscopia. Las pacientes fueron clasificadas en OMA o DE. Se han evaluado datos clínicos como la escala analógica de dolor, demográficos, antropométricos y la escala de calidad de vida SF12V2. Para el análisis estadístico se ha empleado el sistema IBM SPSS 25.0. Resultados: Se han reclutado 307 pacientes, 109 OMA y 198 DE. Las pacientes con OMA son más jóvenes que las pacientes con DE. La calidad de vida en la esfera física es menor en DE que en OMA (46 ± 11,91 vs. 49,9 ± 9,4; p < 0,02). No se han encontrado diferencias significativas en la esfera mental (41,5 ± 10,2 vs. 42,8 ± 11; p < 0,276). No se han encontrado diferencias significativas en los dos grupos en el dolor basado en la escala analógica del dolor. En cambio, en el dominio de dolor de la escala SF12V2, se encontraron diferencias entre OMA y DE, siendo las cifras menores en la profunda (61,4 ± 32,7 vs. 73,6 ± 28,6; p < 0,001). Conclusión: En la práctica clínica se deberían utilizar escalas de calidad de vida porque aportan conocimiento de cómo afecta esta enfermedad a sus vidas. Las pacientes con endometriosis profunda tienen una peor calidad de vida en la esfera física comparada con la de pacientes con endometriosis ovárica aislada.