Restoration of fertility by germ cell, transplantation requires effective recipient preparation
Restoration of fertility by germ cell, transplantation requires effective recipient preparation
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DOI：
10.1095/biolreprod.103.016519
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Orwig, KE
中科院分区：
文献类型：
--
作者：
Brinster, CJ;Ryu, BY;Orwig, KE
精原细胞移植提供了获得哺乳动物种系的机会，并已用于实验动物模型中，以研究干细胞/生态位生物学和种系发育、恢复生育力和产生转基因模型。操纵和/或移植种系的潜力具有许多超越物种界限的实际应用。为了使移植技术更广泛地普及，有必要制定实用的受体准备方案。在目前的研究中，通过在怀孕期间的不同时间用化疗药物白消安治疗怀孕雌性小鼠来准备接受精原细胞移植。供体生殖细胞在产后 5 至 12 天之间被引入雄性后代的睾丸中。对受体动物的分析表明，白消安在交配后 12.5 天对怀孕雌性进行治疗是最有效的；移植了供体生殖细胞的雄性后代变得具有生育能力，并将供体基因型传递给了 25% 的后代。这种方法是有效的，因为1）细胞清除治疗减少（但没有消除）内源性精子发生，为供体干细胞的定植创造了空间，2）残留的内源性生殖细胞有助于形成健康的睾丸环境，支持供体和受体的精子发生，3）经过白消安治疗的胎儿雄性可以作为幼崽进行移植，这些幼崽已被确定为比成年更好的受体。实验室小鼠为开发该技术提供了有价值的实验模型，该技术现在可以在其他物种中应用和评估。
Spermatogonial transplantation provides access to the mammalian germline and has been used in experimental animal models to study stem cell/niche biology and germline development, to restore fertility, and to produce transgenic models. The potential to manipulate and/or transplant the germline has numerous practical applications that transcend species boundaries. To make the transplantation technology more broadly accessible, it is necessary to develop practical recipient preparation protocols. In the current study, mouse recipients for spermatogonial transplantation were prepared by treating pregnant females with the chemotherapeutic agent busulfan at different times during gestation. Donor germ cells were introduced into the testes of male progeny between 5 and 12 days postpartum. Analysis of recipient animals revealed that busulfan treatment of pregnant females on 12.5 days postcoitum was the most effective; male progeny transplanted with donor germ cells became fertile and passed the donor genotype to 25% of progeny. This approach was effective because 1) the cytoablative treatment reduced (but did not abolish) endogenous spermatogenesis, creating space for colonization by donor stem cells, 2) residual endogenous germ cells contributed to a healthy testicular environment that supported robust donor and recipient spermatogenesis, and 3) fetal busulfan-treated males could be transplanted as pups, which have been established as better recipients than adults. Laboratory mice provide a valuable experimental model for developing the technology that now can be applied and evaluated in other species.