In vitro production of functional sperm in cultured neonatal mouse testes
In vitro production of functional sperm in cultured neonatal mouse testes
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DOI：
10.1038/nature09850
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发表时间：
2011-03-24
期刊：
影响因子：
64.8
通讯作者：
Ogawa, Takehiko
中科院分区：
文献类型：
--
作者：
Sato, Takuya;Katagiri, Kumiko;Ogawa, Takehiko
精子发生是体内连续细胞增殖和分化的最复杂和最长的过程之一，从精原干细胞经过减数分裂到精子形成需要一个多月的时间(1,2)。因此，整个过程从未在哺乳动物 (3-5) 和任何其他物种的体外复制，除了某些特定类型的鱼类 (6,7) 之外的极少数例外。在这里，我们证明，仅含有生殖细胞或原始精原细胞作为生殖细胞的新生小鼠睾丸可以在无血清培养基的体外产生精细胞和精子。位于气液界面的组织碎片中的精子发生维持了两个月以上。通过显微授精获得的精细胞和精子产生了健康且具有生殖能力的后代。此外，新生儿睾丸组织被冷冻保存，解冻后在体外显示出完整的精子发生。我们的器官培养方法可以通过进一步完善应用于多种哺乳动物物种，这将作为未来临床应用以及精子发生机制理解的平台。
Spermatogenesis is one of the most complex and longest processes of sequential cell proliferation and differentiation in the body, taking more than a month from spermatogonial stem cells, through meiosis, to sperm formation(1,2). The whole process, therefore, has never been reproduced in vitro in mammals(3-5), nor in any other species with a very few exceptions in some particular types of fish(6,7). Here we show that neonatal mouse testes which contain only gonocytes or primitive spermatogonia as germ cells can produce spermatids and sperm in vitro with serum-free culture media. Spermatogenesis was maintained over 2 months in tissue fragments positioned at the gas-liquid interphase. The obtained spermatids and sperm resulted in healthy and reproductively competent offspring through microinsemination. In addition, neonatal testis tissues were cryopreserved and, after thawing, showed complete spermatogenesis in vitro. Our organ culture method could be applicable through further refinements to a variety of mammalian species, which will serve as a platform for future clinical application as well as mechanistic understanding of spermatogenesis.