Ecto-nucleotidases Activities in the Contents of Ovarian Endometriomas: Potential Biomarkers of Endometriosis

Abstract

Endometriosis, defined as the growth of endometrial tissue outside the uterus, is a common gynecologic condition affecting millions of women worldwide. It is an inflammatory, estrogen-dependent complex disorder, with broad symptomatic variability, pelvic pain, and infertility being the main characteristics. Ovarian endometriomas are frequently developed in women with endometriosis. Late diagnosis is one of the main problems of endometriosis; thus, it is important to identify biomarkers for early diagnosis. The aim of the present work is to evaluate the ecto-nucleotidases activities in the contents of endometriomas. These enzymes, through the regulation of extracellular ATP and adenosine levels, are key enzymes in inflammatory processes, and their expression has been previously characterized in human endometrium. To achieve our objective, the echo-guided aspirated fluids of endometriomas were analyzed by evaluating the ecto-nucleotidases activities and compared with simple cysts. Our results show that enzyme activities are quantifiable in the ovarian cysts aspirates and that endometriomas show significantly higher ecto-nucleotidases activities than simple cysts (5.5-fold increase for ATPase and 20-fold for ADPase), thus being possible candidates for new endometriosis biomarkers. Moreover, we demonstrate the presence of ecto-nucleotidases bearing exosomes in these fluids. These results add up to the knowledge of the physiopathologic mechanisms underlying endometriosis and, open up a promising new field of study.

Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis

“…We had previously quantified ecto‐nucleotidase activity in the same kind of samples . We found that the ecto‐nucleotidase activity was significantly increased in the contents of ovarian endometriomas compared with simple cysts . Coinciding with these findings, we showed significantly higher levels of ENPP1 in endometriomas than in simple cysts.…”

“…We had previously quantified ecto‐nucleotidase activity in the same kind of samples . We found that the ecto‐nucleotidase activity was significantly increased in the contents of ovarian endometriomas compared with simple cysts .…”

“…Blood, urine, and endometrial fluid are the main samples used in order to identify peripheral biomarkers for this pathology . However, follicular fluid has also been validated as a reliable biological fluid to study biomarkers and to discover the underlying causes of the disease …”

“…Therefore, it can modify the immune response and the inflammatory state. In a previous study, we demonstrated that the contents of endometriomas have greater ecto‐nucleotidase activity and CD39 and CD73 protein expression compared with simple cysts; this would contribute to the maintenance of the suppression of local immune responses, basic to the establishment and progression of endometriotic lesions …”

“…As revealed by previous studies, inflammation plays a crucial role in endometriosis pathophysiology and in the endometriotic cell establishment . Purinergic signaling, the group of biological effects mediated by extracellular nucleotides as adenosine triphosphate (ATP) and nucleosides such as adenosine through specific receptors, plays an important role in a wide range of inflammatory conditions and inflammatory diseases .…”