Organoids in polycystic ovary syndrome: Emerging platforms and future directions

Polycystic ovary syndrome (PCOS) is a prevalent and heterogeneous endocrine disorder affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, polycystic ovarian morphology, and metabolic disturbances, including insulin resistance. Despite its high global burden, mechanistic understanding remains incomplete due to limitations of conventional animal models and two-dimensional cultures, which fail to recapitulate the structural organization, endocrine dynamics, and patient-specific variability of human reproductive tissues. Organoid technology has emerged as a transformative platform to bridge this gap. Derived from adult stem cells or pluripotent stem cells, including induced pluripotent stem cells, ovarian and endometrial organoids self-organize into three-dimensional architectures that preserve cellular heterogeneity, hormone responsiveness, and disease-relevant molecular signatures. These systems reproduce key features of PCOS, such as dysregulated steroidogenesis, impaired granulosa-theca cell communication, follicular arrest, progesterone resistance, and oxidative stress-associated dysfunction. Patient-derived organoids further enable investigation of inter-individual heterogeneity and provide platforms for personalized drug testing and biomarker discovery. Integration with bioengineered scaffolds and microfluidic organ-on-chip systems extends modeling capacity to dynamic endocrine feedback and multi-organ interactions, enhancing physiological relevance. Although current organoid platforms do not fully capture systemic neuroendocrine and metabolic complexity, they offer powerful complementary tools for mechanistic interrogation. Collectively, organoid-based approaches redefine experimental modeling in PCOS by linking human-specific tissue biology with translational applications, thereby advancing precision diagnostics and individualized therapeutic strategies.