EVALUATION OF GENOMIC INSTABILITY AND CELL CYCLE IN WOMEN WITH ENDOMETRIOSIS
Endometriosis; Genomic instability; Cell cycle; Infertility; Biomarkers
Endometriosis is a chronic, multifactorial inflammatory gynecological disease that affects approximately 10–15% of women of reproductive age and is associated with chronic pelvic pain, infertility, and impaired quality of life. Recent evidence suggests that genomic instability and cell cycle dysregulation play a central role in the pathophysiology of the disease. This study aimed to evaluate biomarkers of genomic instability (necrosis, apoptosis, micronuclei, nucleoplasmic bridges, and nuclear buds) and alterations in the cell cycle in women with endometriosis, correlating these findings with disease stage, fertility status, hormonal treatment, and the presence of non-communicable chronic diseases (NCDs). This was an observational, cross-sectional study conducted with 83 women diagnosed with endometriosis, who completed a questionnaire to obtain clinical and sociodemographic data and underwent peripheral blood collection for the cytokinesis-block micronucleus (CBMN) assay and analysis of cell cycle phases (G1, S, and G2) by flow cytometry. A negative correlation was observed between endometriosis stage and infertility (ρ = −0.6891; p < 0.05). A lower percentage of cells in the G1 phase was observed in infertile women, and a reduced proportion of cells in the G2 phase was identified in women with NCDs, suggesting impairment of the G1/S and G2/M checkpoints (p <0.05). Additional analyses demonstrated a protective effect of the G1 phase and a positive association between the S phase and the formation of nucleoplasmic bridges, indicating that progression to DNA synthesis in an inflammatory environment favors replicative stress and the formation of structural chromosomal abnormalities. A potentially protective effect of progestin was observed, characterized by a higher frequency of apoptosis and reduced proliferative activity among users, as well as a progressive increase in the proportion of cells in the S phase with increasing disease severity; however, these findings did not reach statistical significance (p > 0.05). Finally, this pioneering study integrating multiple biomarkers of genomic instability and cell cycle parameters in women with endometriosis provides evidence that alterations in genomic stability and cell cycle control may be involved in the pathophysiology of the disease, establishing novel clinical correlations. These findings reinforce the relevance of cellular and molecular approaches to understanding endometriosis as a systemic condition and highlight the potential development of non-invasive biomarkers for diagnosis and clinical monitoring.