{"id":197,"title":"Colonization of allogeneic germline stem cells in mature nonablated mouse testes by inhibition of retinoic acid signaling†","title_zh":"抑制视黄酸信号可让同种异体精原干细胞在未经预处理的成熟小鼠睾丸中定植","url":"https://pubmed.ncbi.nlm.nih.gov/42969836","doi":"10.1093/biolre/ioag244","pmid":"42969836","journal":"Biol Reprod","kind":"paper","lang":"en","published_at":"2026-11-02T00:00:00+00:00","fetched_at":"2026-11-08T03:43:57+00:00","authors":["Morimoto H","Ogonuki N","Matoba S","Pham DQ","Kanatsu-Shinohara M","Yamamoto T","Ogura A","Shinohara T"],"primary_topic":"male","topics":[{"slug":"male","score":7.0,"hits":["spermatogenesis","spermatogonial","testes","testis"]},{"slug":"ivg-stem","score":6.0,"hits":["germline","spermatogonial stem cells","ssc","sscs"]},{"slug":"art-clinical","score":1.0,"hits":["infertile"]},{"slug":"fertility-preservation","score":1.0,"hits":["gonadotoxic"]},{"slug":"repro-tox","score":1.0,"hits":["gonadotoxic"]}],"topic_score":7.0,"preference_score":0.0,"preference_labels":[],"llm_score":78.0,"final_score":78.0,"score_dims":{"novelty":82,"rigor":76,"impact":76,"relevance":90,"translation":68},"recommend_reason":"首次证明药物性（WIN18,446）削弱血睾屏障即可让培养SSC在未预处理、无免疫抑制的同种异体成熟睾丸中定植并产生子代，为自体SSC移植中残留精子发生这一临床难题提供了可操作的药理思路；机制（CLDN3而非CLDN11）尚待细化，且药物安全性需进一步评估。","keywords":["精原干细胞","血睾屏障","视黄酸信号","WIN18,446","同种异体移植","生育力保存"],"selected":1,"story_id":196,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-gametes","source_name":"PubMed · 配子与性腺","source_tier":1,"mention_count":2,"has_interpretation":false,"journal_key":"biolreprod","journal_tier":"standard","journal_if":3.1,"is_mock":false,"summary_zh":"研究以体外培养的小鼠精原干细胞（SSC）为对象，探讨成熟未预处理睾丸中移植定植的屏障机制。结果显示，培养SSC可在Cldn11缺失（血睾屏障受损）睾丸中定植，却无法定植于野生型睾丸，提示血睾屏障（BTB）是主要障碍。ALDH1A2抑制剂WIN18,446抑制视黄酸信号后，虽未下调CLDN11，却引起CLDN3缺失、可能提高BTB通透性，使SSC在无免疫抑制的同种异体受体睾丸中完成精子发生，并经显微授精获得同种异体子代。","summary":"Autologous transplantation of spermatogonial stem cells (SSCs) is a promising approach to restore fertility in young cancer patients who often become infertile due to gonadotoxic treatment. Because only a small number of SSCs can be collected from a biopsy, in vitro expansion of these cells is necessary before auto-transplantation. However, residual spermatogenesis in these patients poses.a significant barrier to efficient colonization of transplanted SSCs. Here, we report that inhibition of retinoic acid signaling by WIN18446, an ALDH1A2 inhibitor, allows colonization of cultured SSCs in nonablated mature testes. Cultured SSCs successfully colonized mouse testes lacking Cldn11-a key molecule for maintaining the blood-testis barrier (BTB)-but failed to colonize wild-type testes, suggesting that the BTB is a major hurdle for colonization. Although WIN18446 treatment did not downregulate CLDN11, it induced a deficiency in CLDN3, possibly through enhancing BTB permeability, and allowed for complete spermatogenesis even in allogeneic recipient testes without immunosuppression. Microinsemination resulted in the production of allogeneic offspring. These results indicate that inhibition of the BTB by WIN18,446 is applicable in cases where endogenous SSCs prevent donor SSC colonization and further demonstrate the unique ability of cultured SSCs to colonize allogeneic testes.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}