Endometriosis affects approximately 10% of reproductive-age women and is associated with genomic instability; however, the contribution of specific DNA repair deficiencies remains poorly understood. This study investigated the expression and function of GEN1, a Holliday junction resolvase critical for homologous recombination, in patient-derived endometrial epithelial organoids (EEOs). Endometrial tissue was obtained by pipelle biopsy from women with laparoscopically confirmed endometriosis (n = 3, stage III–IV) and controls without endometriosis (n = 3). GEN1 mRNA and protein expression were reduced in primary endometrial cells from endometriosis patients compared with controls (mRNA: 0.52 ± 0.14 vs. 1.00 ± 0.19, p = 0.05; immunofluorescence intensity: 0.54 ± 0.18 vs. 1.00 ± 0.22, p = 0.05). Patient-derived EEOs from the endometriosis group showed trends toward lower formation efficiency (18.4 ± 5.6% vs. 25.2 ± 6.8%, p = 0.10) and reduced mean diameter (124.6 ± 34.2 vs. 155.8 ± 32.6 µm, p = 0.10). RNA interference (RNAi)-mediated GEN1 knockdown reduced proliferation in both groups, with a more pronounced effect in endometriosis-derived EEOs (49.7% vs. 39.5% reduction, p = 0.05). Endometriosis-derived EEOs exhibited elevated baseline γH2AX (phosphorylated histone H2AX) immunofluorescence compared with controls (2.32 ± 0.44 vs. 1.00 ± 0.28, p = 0.05), indicating increased DNA double-strand break accumulation. Furthermore, GEN1 knockdown directly increased γH2AX intensity in both groups, with endometriosis-derived EEOs showing a greater absolute increase (Δ1.26 vs. Δ0.72). To our knowledge, this study provides the first organoid-based evidence that GEN1 is downregulated in endometriosis and functionally linked to impaired proliferation and elevated DNA damage, suggesting a potential contribution of homologous recombination dysregulation to endometriosis pathogenesis.

Objective: The study aimed to investigate familial transmission patterns in women with endometriosis by generating a customized single‐nucleotide polymorphism (SNP) array. Methods: Patients aged 18–45 who were diagnosed histopathologically with endometriosis were included in the study. Daughters and mothers of these patients were also included, regardless of whether they were diagnosed with endometriosis or not. The control group consisted of female patients of similar ages who were not diagnosed with endometriosis. The first stage of this investigation was the determination of the genes associated with the SNPs through meta‐analyses in the field of endometriosis in the literature. The second stage was the creation of a unique SNP array by determining the SNPs in the selected target genes. We specifically evaluated whether SNPs in the WNT4 gene at locus 1p36.12 (rs7521902), the GREB1 gene at locus 2p25.1 (rs13391619), and the FN1 gene at locus 2q35 (rs1250248) were associated with endometriosis risk in the Turkish population. Results: The study included 91 participants, comprising 66 women diagnosed with endometriosis and 25 healthy controls. The analysis revealed statistically significant associations for the FN1 (rs1250248, G>A) and the GREB1 (rs13391619, T>C) variants among endometriosis patients and their mothers and daughters, indicating a possible familial genetic link. Conclusion: These findings strengthen the evidence for a hereditary component in endometriosis and suggest that SNP‐based genetic profiling may support earlier identification of at‐risk individuals, enabling more timely surveillance and clinical intervention.

Introduction: Cervical cancer screening through cytology and human papillomavirus (HPV) testing is essential for early detection of precancerous lesions, yet long-term institutional data integrating cytological trends, HPV genotype epidemiology, and diagnostic performance from Turkey remain limited. This study aimed to analyze the distribution and temporal trends of cervical cytological abnormalities, HPV prevalence and genotype distribution, and cytology-histopathology concordance over a 12-year period at a tertiary care center in Istanbul. Methods: A retrospective analysis of all cervical smear samples collected between January 2014 and December 2025 was conducted. Cytology results were classified according to the Bethesda 2014 system. HPV testing, which was performed on a subset of the study population based on clinical indications and kit availability, included mRNA-based assay (Aptima, 2020–2021, n = 4,648) and DNA genotyping (2024–2025, n = 4,308). Cytology-histopathology correlation was assessed for cases with biopsy within 180 days. Results: Among 83,148 cervical smear records, 76,232 evaluable results from women aged ≥21 years were included. The overall epithelial cell abnormality rate was 7.93%, with atypical squamous cells of undetermined significance (5.83%) and low-grade squamous intraepithelial lesions (1.77%) being the most common findings. Epithelial cell abnormality rates varied significantly across age groups, with the highest rate in the 18–20 age group (12.78%) and a significant inverse correlation with increasing age ( r = −0.955, p < 0.001). Among tested patients, HPV positivity was 9.1% by mRNA testing and 9.9% by DNA genotyping, with HPV-16 predominating in both methods (20.5 and 32.8% of positive cases, respectively). Notably, HPV-56 (16.6%) and HPV-51 (14.3%) were more prevalent than HPV-18 (8.9%). High-grade squamous intraepithelial lesion cytology demonstrated a positive predictive value of 89.2% for detecting cervical intraepithelial neoplasia grade 2 or higher. A significant decrease in epithelial cell abnormality rates was observed over the study period ( r = −0.591, p = 0.043), with a more pronounced decline in high-grade abnormalities ( r = −0.911, p < 0.001). Conclusion: The 12-year analysis shows a decrease in cervical cytological abnormalities and provides valuable epidemiological data on HPV genotype distribution in a Turkish population. The high prevalence of non-vaccine-targeted genotypes, such as HPV-56 and HPV-51, should be considered in future vaccination strategies.