Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice
Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice
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DOI：
10.1073/pnas.1211845109
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发表时间：
2012-10-16
影响因子：
11.1
通讯作者：
Ogawa, Takehiko
中科院分区：
文献类型：
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作者：
Sato, Takuya;Yokonishi, Tetsuhiro;Ogawa, Takehiko
男性不育症最常见的原因是生精缺陷或不育，其中大多数是尚未治愈的。最近，我们成功地培养了小鼠睾丸组织，用于从精原干细胞产生可育精子。在这里，我们表明，最严重的类型之一的精子发生缺陷突变体可以治疗的文化方法，没有任何遗传操作。S1/S1（d）小鼠被用作这种雄性不育的模型。Sl/Sl（d）小鼠的睾丸仅具有原始精原细胞作为生殖细胞，由于c-kit配体（KITL）基因突变导致支持细胞表面膜结合型KITL的丢失而缺乏精子发生的任何迹象。为了弥补这一缺陷，我们用含有重组KITL的培养基培养Sl/Sl（d）小鼠的睾丸组织，发现它诱导精原细胞分化直至减数分裂结束。我们进一步发现集落刺激因子-1（CSF-1）增强KITL的作用，并促进精子发生直至精子的产生。单倍体细胞的显微授精导致了健康后代的分娩。这项研究表明，生精障碍可以通过补充原始睾丸中不足的某些因子或物质进行体外治疗。
Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, we show that one of the most severe types of spermatogenic defect mutant can be treated by the culture method without any genetic manipulations. The Sl/Sl(d) mouse is used as a model of such male infertility. The testis of the Sl/Sl(d) mouse has only primitive spermatogonia as germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the surface of Sertoli cells. To compensate for the deficit, we cultured testis tissues of Sl/Sl(d) mice with a medium containing recombinant KITL and found that it induced the differentiation of spermatogonia up to the end of meiosis. We further discovered that colony stimulating factor-1 (CSF-1) enhances the effect of KITL and promotes spermatogenesis up to the production of sperm. Microinsemination of haploid cells resulted in delivery of healthy offspring. This study demonstrated that spermatogenic impairments can be treated in vitro with the supplementation of certain factors or substances that are insufficient in the original testes.