Induced pluripotent stem cells in modeling polycystic ovarian syndrome: Unveiling pathogenesis, cellular communication, and therapeutic potential through a focus on multi-lineage differentiation potential and extracellular vesicle profiling

Understanding polycystic ovary syndrome (PCOS) remains a major challenge in reproductive medicine. Affecting up to 20% of reproductive-age women, it involves disrupted neuroendocrine regulation, excessive androgen production, metabolic dysfunction, and insulin resistance, also leading to infertility. These abnormalities stem from complex interactions between gonadotropin-releasing hormone neurons, ovarian granulosa cells, and adipose tissue. Additionally, impaired endometrial stromal cell function worsens fertility issues. The STEM-O project will generate induced pluripotent stem cell (iPSC) lines from women with PCOS and high polygenic risk scores, identified via genome-wide association studies (GWAS), alongside low-risk controls. Differentiating iPSC into neurons, ovarian granulosa cells, and adipocytes we will provide insights into PCOS etiology. The project will also examine extracellular vesicles, along cell differentiation, advancing understanding of PCOS pathogenesis.