Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice
Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice
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DOI：
10.1073/pnas.022646399
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发表时间：
2002-02-05
影响因子：
11.1
通讯作者：
Shinohara, T
中科院分区：
文献类型：
--
作者：
Kanatsu-Shinohara, M;Ogura, A;Shinohara, T
支持细胞通过与生殖细胞的相互作用在精子发生中起关键作用。为了建立一种治疗支持细胞功能障碍所致雄性不育的策略，我们利用腺病毒载体建立了一种支持细胞基因转移系统，该系统在不育小鼠睾丸中保持转基因的长期表达。将携带小鼠Steel（Sl）基因的腺病毒导入支持细胞，恢复了不育Steel/Steel（dickie）（Sl/Sl（d））突变小鼠睾丸的部分精子发生。虽然这些雄性动物仍然不育，但圆形精子细胞和睾丸精子在卵母细胞胞浆内注射后产生了正常的可育后代。没有一个后代显示出腺病毒DNA的生殖系传播的证据。因此，我们证明了通过使用基因治疗载体成功治疗不育症。因此，腺病毒介导的基因递送到支持细胞中不仅提供了一种通过操纵体内生殖细胞微环境来研究生殖细胞-支持细胞相互作用的有效和方便的手段，而且是治疗由支持细胞缺陷引起的男性不育症的有用方法。
Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysf unction, we developed a Sertoli cell gene transfer system by using an adenovirus vector, which maintained long-term transgene expression in the testes of infertile mice. Introduction of an adenovirus carrying the mouse Steel (Sl) gene into Sertoli cells restored partial spermatogenesis in infertile Steel/Steel(dickie) (Sl/Sl(d)) mutant mouse testes. Although these males remained infertile, round spermatids and spermatozoa from the testes produced normal fertile offspring after intracytoplasmic injection into oocytes. None of the offspring showed evidence of germ line transmission of adenoviral DNA. Thus, we demonstrate a successful treatment for infertility by using a gene therapy vector. Therefore, adenovirus-mediated gene delivery into Sertoli cells not only provides an efficient and convenient means for studying germ cell-Sertoli cell interactions through manipulation of the germ cell microenvironment in vivo, but also is a useful method to treat male infertility resulting from a Sertoli cell defect.