Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease

Abstract Endometriosis is an estrogen-dependent disease defined by the presence and growth of functional endometrial-like tissue, glands and stroma, outside the uterine cavity. Macrophages are broadly classified into pro-inflammatory M1 macrophages, and M2 macrophages, which have selective anti-inflammatory and pro-fibrotic activities and are able to induce immunotolerance and angiogenesis. Based on these elements, the aim of our study was to evaluate CD14+CD68+CD197+CD80+ M1 and CD14+CD68+CD163+CD206+ M2 macrophages in tissue samples from ovarian endometriomas of women affected by endometriosis at different stages of the disease. For each patient, we collected a biological sample of the cyst (ovarian endometriomas for cases and ovarian functional cyst for controls) during laparoscopy. We found that the number of both M1 and M2 macrophages was significantly higher in endometriosis group than controls, regardless of stage (p < .0001 for each stage versus controls). Moreover, our data analysis shows a trend in progressive decrease of M1 macrophages from stage I to stage IV; on the contrary, M2 macrophages show a specular trend compared to M1 macrophages, with a progressive increase from stage I to stage IV. This may contribute to the pro-inflammatory microenvironment in the early stages of the disease, and to the pro-fibrotic activity of the advanced stages.

[1]  F. Reis,et al.  B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice. , 2019, Human reproduction.

[2]  S. Robertson,et al.  Macrophages infiltrating endometriosis-like lesions exhibit progressive phenotype changes in a heterologous mouse model. , 2019, Journal of reproductive immunology.

[3]  A. Peiris,et al.  Endometriosis. , 2018, JAMA.

[4]  Hua He,et al.  Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway , 2018, Journal of immunology research.

[5]  M. Kaplan,et al.  M1 Macrophages but Not M2 Macrophages Are Characterized by Upregulation of CRP Expression via Activation of NFκB: a Possible Role for Ox-LDL in Macrophage Polarization , 2018, Inflammation.

[6]  P. Vercellini,et al.  Time to redefine endometriosis including its pro-fibrotic nature , 2018, Human reproduction.

[7]  L. Giudice,et al.  World Endometriosis Society consensus on the classification of endometriosis , 2017, Human reproduction.

[8]  Oliver Sawodny,et al.  Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages , 2016, PLoS Comput. Biol..

[9]  Yukio Fujiwara,et al.  Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy. , 2016, Advanced drug delivery reviews.

[10]  Phillip G. Popovich,et al.  Novel Markers to Delineate Murine M1 and M2 Macrophages , 2015, PloS one.

[11]  G. B. Buck Louis,et al.  World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research , 2014, Fertility and sterility.

[12]  Klaus Ley,et al.  M1 and M2 Macrophages: The Chicken and the Egg of Immunity , 2014, Journal of Innate Immunity.

[13]  S. Verbruggen,et al.  Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo , 2013, Angiogenesis.

[14]  Sabine Van Huffel,et al.  Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group , 2010, BMJ : British Medical Journal.

[15]  S. Ferrari,et al.  Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease. , 2009, The American journal of pathology.

[16]  D. Timmerman,et al.  High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. , 2009, Fertility and sterility.

[17]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2008, Journal of clinical epidemiology.

[18]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2007, Preventive medicine.

[19]  L. Muzii,et al.  Laparoscopic excision of ovarian cysts: is the stripping technique a tissue-sparing procedure? , 2002, Fertility and sterility.

[20]  M. Canis,et al.  Revised American Society for Reproductive Medicine classification of endometriosis: 1996. , 1997, Fertility and sterility.