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Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis

Departament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, Campus Bellvitge, Universitat de Barcelona, 08907 Barcelona, Spain
Oncobell Program, CIBERONC, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
Servei d’Anatomia Patològica, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain
Servei de Ginecologia, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain
Salud de la Mujer Dexeus, Hospital Universitari Quiron Dexeus, 08028 Barcelona, Spain
Centre de Recherche du CHU de Québec - Université Laval, Québec City, QC G1V 4G2, Canada
Départment de Microbiologie-Infectiologie et d’Immunologie, Faculté de Médecine, Université Laval, Quebec City, QC G1V 4G2, Canada
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5532;
Received: 16 September 2019 / Revised: 28 October 2019 / Accepted: 2 November 2019 / Published: 6 November 2019
(This article belongs to the Special Issue Endometriosis Research: From Bench to Bedside)
Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis. View Full-Text
Keywords: endometriosis; endometrium; uterus; purinergic signaling; ATP endometriosis; endometrium; uterus; purinergic signaling; ATP
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Trapero, C.; Vidal, A.; Fernández-Montolí, M.E.; Coroleu, B.; Tresserra, F.; Barri, P.; Gómez de Aranda, I.; Sévigny, J.; Ponce, J.; Matias-Guiu, X.; Martín-Satué, M. Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis. Int. J. Mol. Sci. 2019, 20, 5532.

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