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タイトル: | Autologous transplantation of spermatogonial stem cells restores fertility in congenitally infertile mice |
著者: | Kanatsu-Shinohara, Mito Ogonuki, Narumi Matoba, Shogo Ogura, Atsuo Shinohara, Takashi |
著者名の別形: | 篠原, 美都 越後貫, 成美 的場, 章悟 小倉, 淳郎 篠原, 隆司 |
キーワード: | claudin Sertoli cell spermatogenesis |
発行日: | 7-Apr-2020 |
出版者: | National Academy of Sciences |
誌名: | Proceedings of the National Academy of Sciences of the United States of America |
巻: | 117 |
号: | 14 |
開始ページ: | 7837 |
終了ページ: | 7844 |
抄録: | The blood–testis barrier (BTB) is thought to be indispensable for spermatogenesis because it creates a special environment for meiosis and protects haploid cells from the immune system. The BTB divides the seminiferous tubules into the adluminal and basal compartments. Spermatogonial stem cells (SSCs) have a unique ability to transmigrate from the adluminal compartment to the basal compartment through the BTB upon transplantation into the seminiferous tubule. Here, we analyzed the role of Cldn11, a major component of the BTB, in spermatogenesis using spermatogonial transplantation. Cldn11-deficient mice are infertile due to the cessation of spermatogenesis at the spermatocyte stage. Cldn11-deficient SSCs failed to colonize wild-type testes efficiently, and Cldn11-deficient SSCs that underwent double depletion of Cldn3 and Cldn5 showed minimal colonization, suggesting that claudins on SSCs are necessary for transmigration. However, Cldn11-deficient Sertoli cells increased SSC homing efficiency by >3-fold, suggesting that CLDN11 in Sertoli cells inhibits transmigration of SSCs through the BTB. In contrast to endogenous SSCs in intact Cldn11-deficient testes, those from WT or Cldn11-deficient testes regenerated sperm in Cldn11-deficient testes. The success of this autologous transplantation appears to depend on removal of endogenous germ cells for recipient preparation, which reprogrammed claudin expression patterns in Sertoli cells. Consistent with this idea, in vivo depletion of Cldn3/5 regenerated endogenous spermatogenesis in Cldn11-deficient mice. Thus, coordinated claudin expression in both SSCs and Sertoli cells expression is necessary for SSC homing and regeneration of spermatogenesis, and autologous stem cell transplantation can rescue congenital defects of a self-renewing tissue. |
記述: | 精子幹細胞の自家移植により先天性男性不妊症が回復することを発見 --先天性不妊症にも柔軟性--. 京都大学プレスリリース. 2020-04-08. |
著作権等: | This is a postprint of the article, which has been published in final form at https://doi.org/10.1073/pnas.1914963117. The full-text file will be made open to the public on 7 October 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/250237 |
DOI(出版社版): | 10.1073/pnas.1914963117 |
PubMed ID: | 32229564 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2020-04-08 |
出現コレクション: | 学術雑誌掲載論文等 |
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