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While in vitro culture of prepubertal testis tissue offers a potential solution to preserve fertility, producing sufficient sperm remains a major barrier. To address this, we developed a hydrogel microneedle\u2010based culture system, which is used to culture mouse testes from 5 days postpartum (d\n                    <jats:italic>pp<\/jats:italic>\n                    ) and establish a model of \u2018whole testicular spermatogonia pool\u2019 (WTSP). This system promotes over fourfold expansion of undifferentiated spermatogonia, compared to declining numbers during in vivo development. Transplantation of WTSP into nude mice doubled spermatids count per tubule compared to conventional whole testes transplantation. Furthermore, in vitro meiosis induction of WTSP significantly enhanced spermatid proportion, thus generating fertile offspring. Using this system, we\u00a0also cultured the gonads harvested from aborted human male fetuses and observes significant proliferation of spermatogonia. Lastly, it is shown that the cellular states of the WTSP closely resemble those of 5 d\n                    <jats:italic>pp<\/jats:italic>\n                    mouse testes, and the role of EPHA2 in promoting spermatogonia proliferation by activating the PI3K\u2010AKT\u2010mTOR pathway. In conclusion, the WTSP offers a promising method for preserving fertility in prepubertal male cancer patients by maintaining and expanding spermatogonia extracted before treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202502435","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:45:11Z","timestamp":1753699511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Cultivation System for Germ Cell Proliferation and Sustaining Whole Testicular Niche"],"prefix":"10.1002","volume":"12","author":[{"given":"Yu","family":"Xia","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University  Nanjing Jiangsu 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing 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