Dysregulated Telomere Dynamics and Molecular Alterations in Cumulus and Granulosa Cells of Patients with Polycystic Ovary Syndrome

Background: Telomere length and the shelterin proteins telomeric repeat-binding factor 1 (TRF1) and telomeric repeat-binding factor 2 (TRF2) are key regulators of telomere dynamics and cellular homeostasis. We investigated telomere length, the expression of shelterin proteins, and apoptotic markers in cumulus cells and granulosa cells from patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment. Methods: Cumulus and granulosa cells were collected from sixty-five patients with and without PCOS. Telomere length was measured by quantitative polymerase chain reaction (qPCR), and TRF1, TRF2 and apoptotic markers were analyzed by qPCR and immunofluorescence. Results: Telomere length was significantly reduced in granulosa cells from patients with PCOS (p < 0.0001), whereas no differences between the two groups were observed in cumulus cells (p = 0.14). Bcl-2-associated X (BAX) gene expression was increased in both cell types from patients with PCOS. Immunofluorescence analysis revealed a higher number of TRF1 nuclear spots in cumulus cells from patients with PCOS (p < 0.001), while mRNA expression did not differ (p = 0.68). No differences were detected in granulosa cells for TRF1 by either immunofluorescence (p = 0.61) or qPCR (p = 0.17) between PCOS and control patients. TRF2 nuclear spots were reduced in cumulus cells (p < 0.001), accompanied by increased messenger RNA expression (p < 0.01), whereas in granulosa cells, mRNA expression was higher compared to the control (p < 0.05), with no change in nuclear localization (p = 0.68). Conclusions: These findings indicate that PCOS is associated with altered telomere length and dysregulated expression and localization of shelterin proteins in ovarian somatic cells.