Models of germ cell development and their application for toxicity studies.
Models of germ cell development and their application for toxicity studies.
复制标题
生殖细胞发育的模型及其在毒性研究中的应用。
DOI：
10.1002/em.21946
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发表时间：
2015-10
影响因子：
2.8
通讯作者：
Allard P
中科院分区：
文献类型：
--
作者：
Ferreira DW;Allard P
生殖细胞具有将遗传信息和性状代代相传的独特能力。因此，生殖细胞的正常发育及其基因组的完整性对生物体的健康和物种的生存至关重要。生殖细胞对环境影响也非常敏感，尽管生殖细胞毒性的测试，特别是在女性中，已经证明特别具有挑战性。在这篇综述中，我们首先描述了显着的奥德赛的生殖细胞在哺乳动物中，重点是女性生殖系，从他们的初始规格在胚胎发育过程中的成熟配子在成人的一代。我们还描述了目前用于生殖细胞毒性试验的方法及其在研究哺乳动物生殖细胞发育的复杂特征方面的局限性。为了绕过这些挑战，我们建议使用替代模型系统，如酿酒酵母，果蝇，秀丽隐杆线虫和体外生殖细胞方法，具有明显的优势，比传统的毒性模型。我们讨论了每种方法的优点和局限性，它们在生殖细胞毒性研究中的应用，以及需要计算方法来最大限度地提高这些模型的实用性。总之，纳入这些替代生殖细胞毒性模型对于检查哺乳动物中不易进入的阶段以及生殖细胞毒性的大规模高通量研究将是非常宝贵的。
Germ cells are unique in their ability to transfer genetic information and traits from generation to generation. As such, the proper development of germ cells and the integrity of their genome are paramount to the health of organisms and the survival of species. Germ cells are also exquisitely sensitive to environmental influences although the testing of germ cell toxicity, especially in females, has proven particularly challenging. In this review, we first describe the remarkable odyssey of germ cells in mammals, with an emphasis on the female germline, from their initial specification during embryogenesis to the generation of mature gametes in adults. We also describe the current methods used in germ cell toxicity testing and their limitations in examining the complex features of mammalian germ cell development. To bypass these challenges, we propose the use of alternative model systems such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and in vitro germ cell methods that have distinct advantages over traditional toxicity models. We discuss the benefits and limitations of each approach, their application to germ cell toxicity studies, and the need for computational approaches to maximize the usefulness of these models. Together, the inclusion of these alternative germ cell toxicity models will be invaluable for the examination of stages not easily accessible in mammals as well as the large scale, high-throughput investigation of germ cell toxicity.