SIRT6 is a mammalian deacetylase associated with the pathogenesis of endometriosis.

DOI: 10.1055/s-0045-1812525 SIRT6 is a mammalian deacetylase associated with the pathogenesis of endometriosis. Authors Topic: Gynäkologische Endokrinologie und Reproduktionsmedizin Einleitung: Sirtuin 6 (SIRT6) is a chromatin-associated enzyme involved in DNA repair, inflammation, and metabolic homeostasis. Altered SIRT6 expression has been linked to various inflammatory diseases, yet its role in endometriosis remains unclear. Patient:innen und Methoden Tissue samples were collected from premenopausal women (18-50 years) undergoing laparoscopic surgery for histologically confirmed endometriosis (n=72) and for non-endometriosis-related benign gynaecological conditions (n=37) in accordance to the Declaration of Helsinki and under Institutional Ethics Committee approval of the Medical University of Vienna (EK545/2010). SIRT6 mRNA levels were assessed by quantitative RT-PCR using total tissue RNA extracts and the SIRT6 protein levels were analysed using immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue sections. Epithelial and stromal SIRT6 protein levels were quantified as percent positive cells over an area of 5 different fields (0.25mm2) at 200x magnification. Clinical parameters and lifestyle factors were recorded and included in the analysis. Ergebnisse: The q-PCR analysis showed that SIRT6 is a differentially expressed, up-regulated gene in endometrium of women with, compared to women without endometriosis (adjp=0.0052), suggesting a functional relevance of the gene in the pathogenesis of the disease. IHC analysis revealed that SIRT6 is expressed in both epithelial and stromal cells of analysed tissue, with stroma cells showing only nuclear and epithelial cells nuclear and cytosolic SIRT6 expression. Stromal SIRT6 expression exhibited a remarkable increase in eutopic endometrium (30-fold; adjp=0.00012) and significant, but less pronounced up-regulation in ectopic lesions (adjp=0.0181), compared to controls. The eutopic upregulation was especially evident in proliferative endometrium (adjp=0.0219), in younger patients with BMI≥25 (adjp=0.0231), in patients with lower disease RAFs-score (adjp=0.0434) and in physically inactive individuals (adjp=0.0025). The levels of stromal SIRT6 protein were independent of fertility status and smoking. Schlussfolgerung/Diskussion: Our findings suggest that SIRT6 is a mammalian deacetylase associated with the pathogenesis of endometriosis, which may have different cellular functions in stromal and epithelial cells of endometriosis tissues. SIRT6 stromal cell deregulation in proliferative endometrium of women with the disease could be associated with endometrial inflammation. This idea is supported by the findings that the enzyme is significantly up-regulated in women with high BMI and in physically inactive individuals. Publication History Article published online: 12 November 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany