Stem Cell-Based Testicular Organoids: An Advanced Approach for Testis Regeneration and Male Infertility Treatment: A Systematic Review

Introduction: Male infertility affects ۱۵–۲۰% of couples worldwide, posing a significant global health challenge. Conventional approaches like ۲D (۲ Dimentional) cell cultures and animal models have limited ability to replicate the complex structure, cellular diversity, and microenvironment of the human testis. Stem cell-derived testicular organoids, as three-dimensional in vitro systems, better recapitulate spermatogenesis and testicular function. This systematic review evaluates the development, characterization, and applications of stem cell-based testicular organoids for testis regeneration and male infertility treatment from January ۲۰۱۸ to June ۲۰۲۵.Methods: Conducted per PRISMA ۲۰۲۰ guidelines (PROSPERO ID: ۱۱۷۲۵۸۱), this review searched PubMed, Scopus, Web of Science, and Embase for studies using embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or spermatogonial stem cells (SSCs) to develop testicular organoids. Methodological quality was assessed using a modified SYRCLE risk of bias tool.Results: A total of ۴۶ studies from Europe, North America, and Asia were reviewed, showcasing diverse culture systems and stem cell sources. Organoids demonstrated marker expression of ۹۲.۳% for primordial germ cells, ۸۷.۲% for SSCs, ۵۷.۷% for meiotic cells, and ۴۱.۰% for post-meiotic cells (n=۷). CRISPR-Cas۹ genetic engineering exhibited low genotoxicity while preserving reproductive potential. Microfluidic “testis-on-a-chip” systems-maintained tissue organization and hormone secretion for ۲–۷ weeks. Applications included modeling testicular germ cell tumors, testing toxicants (e.g., busulfan, TiO₂ nanoparticles), and evaluating fertility-protective agents like Coenzyme Q۱۰.Conclusion: Stem cell-derived testicular organoids, integrated with CRISPR technology, microfluidics, and toxicological assays, provide advanced platforms for studying male infertility. These systems reduce reliance on animal models and pave the way for therapeutic innovation and personalized reproductive medicine.

کلیدواژه ها:

Testicular Organoids ، spermatogenesis ، Male infertility ، stem cells ، CRISPR-Cas۹ ، microfluidics ، Reproductive Medicine