Organoids and organ‐on‐a‐chip models for investigating the pathophysiology of the human reproductive system

Abstract Organoids and organ‐on‐a‐chips (OoCs), as innovative tools that overcome the limitations of traditional cell and animal models, provide highly biomimetic platforms for studying the pathophysiological mechanisms of the reproductive system. This review emphasizes mechanistic discoveries, disease models, and translational prospects. In contrast to previous reviews that either addressed organoids and OoCs separately or concentrated on a single organ type, this article is unique in that it (i) integrates OoC and organoid platforms for both male and female reproductive systems; (ii) identifies four cross‐cutting scientific challenges (vascularization/perfusion, dynamic endocrine modeling, immune‐microenvironment reconstruction, and model standardization); and (iii) highlights translational pathways, such as artificial intelligence—enabled optimization and organoid‐derived extracellular vesicles. We summarize representative organoid and OoC models of key male (testis, prostate, and epididymis) and female (ovary, endometrium, and placenta) reproductive organs, and discuss prospects for multi‐organ integration, personalized drug testing, and regulatory standardization. Finally, we propose prioritized technological milestones and a roadmap to expedite the clinical translation of these technologies in reproductive system research.