Differential expression of microRNAs after induction of endometriosis in baboons†.

Endometriosis is an inflammatory chronic gynecological condition that affects 10-15% of reproductive-age women which causes pelvic pain and infertility. The disease is characterized by the growth of endometrial tissue outside the uterine cavity. Currently, early diagnosis of endometriosis is difficult due to non-specific symptoms and the absence of reliable biomarkers. Understanding these early molecular alterations could support the development of diagnostic tools for timely detection and treatment. The objective of this study was to identify changes in circulating microRNA (miRNA) profiles during the initial stages of endometriosis using a longitudinal non-human primate baboon model. Endometriosis was induced in female baboons by laparoscopic inoculation of menstrual endometrial tissue and plasma was collected at various timepoints. Plasma miRNAs at 3, 6, 9, and 15 months were analyzed using RNA sequencing. A total of 2731 miRNAs were detected, 76 of which showed significant differences at least at one time point. There are four, three, and one miRNA exclusively differentially expressed at 3-, 6- and 9-month timepoints, respectively, and 68 miRNAs at 15 months. Four miRNAs (miR-210-3p, miR-448, miR-1260a/1260b, and miR-1298-5p) exhibited significant alterations across all time points. Of these, miR-210-3p increased, while the others decreased significantly. Hierarchical clustering revealed separation between the early (pre-inoculation and 3 months) and late (3 and 15 months) stages, indicating progressive divergence of miRNA profiles. These findings identify candidate miRNAs that may provide insight into early pathophysiological mechanisms and represent candidate circulating biomarkers associated with temporal molecular changes following disease induction, warranting further validation.