RESUMEN
MLLT11 is a gene implicated in cell differentiation and the development and progression of human cancers, but whose role in the pathogenesis of endometriosis is still unknown. Using quantitative RT-PCR and immunohistochemistry, we analyzed 37 women with and 33 women without endometriosis for differences in MLLT11 expression. We found that MLLT11 is reduced in the ectopic stroma cells of women with advanced stage endometriosis compared to women without endometriosis. MLLT11 knockdown in control stroma cells resulted in the downregulation of their proliferation accompanied by G1 cell arrest and an increase in the expression of p21 and p27. Furthermore, the knockdown of MLLT11 was associated with increased apoptosis resistance to camptothecin associated with changes in BCL2/BAX signaling. Finally, MLLT11 siRNA knockdown in the control primary stroma cells led to an increase in cell adhesion associated with the transcriptional activation of ACTA2 and TGFB2. We found that the cellular phenotype of MLLT11 knockdown cells resembled the phenotype of the primary endometriosis stroma cells of the lesion, where the levels of MLLT11 are significantly reduced compared to the eutopic stroma cells of women without the disease. Overall, our results indicate that MLLT11 may be a new clinically relevant player in the pathogenesis of endometriosis.
Asunto(s)
Endometriosis , Femenino , Humanos , Adhesión Celular/genética , Endometriosis/genética , Genes Reguladores , Factores de Transcripción , Proliferación Celular/genética , Proteínas de Neoplasias , Proteínas Proto-OncogénicasRESUMEN
Background: Fatigue is mentioned as one of the most significant symptoms of endometriosis. The impact of laparoscopic endometriosis surgeries on fatigue remains unknown. The aim of this study was to investigate, for the first time, the effect of laparoscopic surgery in endometriosis patients, with the complete removal of endometriotic lesions, on the severity of fatigue. Methods: This is a single-center prospective pilot study including 58 participants. Participants were recruited at the Tertiary Endometriosis Referral Center of the Medical University of Vienna between February 2020 and November 2021. Thirty patients with histologically proven endometriosis were compared to a control group of 28 patients who underwent a laparoscopy for benign gynecologic conditions other than endometriosis. All participants were interviewed using the Fatigue Severity Scale before their surgery and 6 months afterward. Relationships between variables were established using regression analysis and associations were quantified as odds ratios. Results: Fatigue was significantly more severe preoperatively in patients with endometriosis when compared to controls ((odds ratio (OR): 1.82; 95% confidence interval (CI): 1.24-2.67, p < 0.01). Six months postoperatively, the fatigue severity score of endometriosis patients decreased significantly (p < 0.01). In multivariate analysis, fatigue was significantly associated with endometriosis (OR: 4.50, CI: 1.14-17.8, p < 0.05), when adjusted for abdominal pain and menstrual bleeding. Fatigue in patients with endometriosis was not associated with disease stage or the presence of deep endometriosis. Conclusions: Fatigue is a frequent and bothersome symptom in patients with endometriosis. Within our study, we demonstrated for the first time that fatigue responds to surgical treatment. The management of fatigue is crucial to improving patients' quality of life.