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.

a Equal contributors. b These authors jointly supervised this work. AbstractMacrophages play an important role in the inflammatory response. Their various biological functions are induced by different membrane receptors, including Toll-like receptors, which trigger several intracellular signaling cascades and activate the inflammasomes, which in turn elicit the release of inflammatory mediators such as cytokines. In this study, we present a novel method for the isolation of human mature peritoneal macrophages. This method can be easily implemented by gynecologists who routinely perform laparoscopy for sterilization by tubal ligation or surgically intervene in benign gynecological pathologies. Our method confirms that macrophages are the main peritoneal leukocyte subpopulation isolated from the human peritoneum in homeostasis. We showed that primary human peritoneal macrophages present phagocytic and oxidative activities, and respond to activation of the main proinflammatory pathways such as Toll-like receptors and inflammasomes, resulting in the secretion of different proinflammatory cytokines. Therefore, this method provides a useful tool for characterizing primary human macrophages as control cells for studies of molecular inflammatory pathways in steady-state conditions and for comparing them with those obtained from pathologies involving the peritoneal cavity. Furthermore, it will facilitate advances in the screening of anti-inflammatory compounds in the human system.

Endometriosis is a multifactorial disease with pathophysiological factors not yet well known; it also presents a wide symptomatic range that makes us think about the need for multidisciplinary management. It is a chronic disease in which there is no definitive treatment, and is associated in a large majority of cases with psychological pathology. Connecting comorbidities and multimorbidities on a neurobiological, neuropsychological, and pathophysiological level could significantly contribute to their more successful prevention and treatment. In our study, resilience is analyzed as an adjunctive measure in the management of endometriosis. Methods: A multi-centre, cross-sectional study was performed to analyse resilience levels in a sample of Spanish women suffering from endometriosis. CDRIS-25, CDRIS-10, BDI, the STAI, and the SF-36 Health Questionnaire were used for assessments. A representative group of 202 women with endometriosis was recruited by consecutive sampling. Exploratory and confirmatory factor analyses were performed for both resilience scales. Results: Mean CDRIS-25 and CDRIS-10 scores were 69.58 (SD 15.1) and 29.37 (SD 7.2), respectively. Women with adenomyosis and without signs of deep endometriosis showed the lowest scores. The best predictive model included women’s age, years of endometriosis evolution, number of pregnancies, and history of fertility problems as the best predictive factors. Conclusions: Women build resilience as the number of years of evolution of the disease increases. Symptoms such as dyspareunia and continued abdominal pain were more prevalent among less resilient women.

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Six months following surgery, the results were entirely satisfactory, with full urinary continence and significant improvement in the patient's quality of life. A discussion about controversial approaches to diagnosis and management is included.