MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis

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RESEARCH

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MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis Piotr Laudanski1*, Radoslaw Charkiewicz2, Mariusz Kuzmicki3, Jacek Szamatowicz3, Alicja Charkiewicz4 and Jacek Niklinski2

Abstract Background: The eutopic endometrium of women with endometriosis, compared with disease-free individuals, contains certain molecular alterations, including the differential expression of microRNA (miRNA). The aim of the study was to compare the expression of the most relevant miRNAs in the eutopic endometrium of women with and without ovarian endometriosis. Methods: A total of 46 regularly menstruating patients, 21 patients with ovarian endometriosis and 25 controls, underwent surgery in the proliferative phase of the cycle. The eutopic endometrium was collected through aspirating biopsy prior to laparoscopy. Only patients with advanced (stage III and IV) histopathologically confirmed ovarian endometriosis were included. TaqMan MicroRNA Array Cards were applied to examine the expression of 667 human miRNAs in 10 patients with endometriosis and 10 controls. Custom-made, low-density real-time PCR arrays were used to confirm the expression of 15 selected molecules in 21 endometriosis patients and 25 diseasefree individuals. Results: Of 667 miRNAs, 2 were highly likely to be upregulated and 13 were downregulated in the eutopic endometrium of patients with endometriosis compared with the controls. Validation using real-time PCR showed that hsa-miR-483-5p (p = 0.012) and hsa-miR-629* (p = 0.02) are significantly downregulated in patients with endometriosis. Conclusions: Changes in the expression of select miRNAs might lead to or be a consequence of an early defect in the physiological activity of the proliferative endometrium, ultimately resulting in the overgrowth of this tissue outside the uterus. Keywords: Endometriosis, Eutopic endometrium, MiRNAs

Background Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. It represents a widespread condition with a relevant impact on women’s health. The pathogenesis of endometriosis remains unclear. More than 80 years ago, it was hypothesised that endometriosis might arise from an ectopic implant of endometrial cells in the peritoneum of the pelvic cavity after retrograde menstruation [1]. This theory is, however, * Correspondence: [email protected] 1 Department of Perinatology, Medical University of Bialystok, ul. Marii Sklodowskiej-Curie 24a, 15-276, Bialystok, Poland Full list of author information is available at the end of the article

questionable because the backward passage of endometrial cells along the fallopian tubes is a physiological process that occurs in most women during normal menstruation [2]. Thus, it has subsequently been suggested that the ectopic implant of endometrial cells after passage through the fallopian tubes might also be facilitated through a disturbed immunological status, reflected through the altered status of different biologically active sub