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使用人类组织和细胞的睾丸发育和功能的实验模型。

Experimental models of testicular development and function using human tissue and cells.

机构信息

MRC Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.

Department of Growth and Reproduction, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

出版信息

Mol Cell Endocrinol. 2018 Jun 15;468:95-110. doi: 10.1016/j.mce.2017.12.011. Epub 2018 Jan 6.

Abstract

The mammalian testis has two main roles, production of gametes for reproduction and synthesis of steroid- and peptide hormones for masculinization. These processes are tightly regulated and involve complex interactions between a number of germ and somatic cell-types that comprise a unique microenvironment known as the germ stem cell niche. In humans, failure of normal testicular development or function is associated with susceptibility to a variety of male reproductive disorders including disorders of sex development, infertility and testicular cancer. Whilst studies in rodent models have provided detailed insight into the signaling pathways and molecular mechanisms that regulate the testis, there are important species differences in testicular development, function and reproductive disorders that highlight the need for suitable experimental models utilising human testicular tissues or cells. In this review, we outline experimental approaches used to sustain cells and tissue from human testis at different developmental time-points and discuss relevant end-points. These include survival, proliferation and differentiation of cell lineages within the testis as well as autocrine, paracrine and endocrine function. We also highlight the utility of these experimental approaches for modelling the effects of environmental exposures on testicular development and function.

摘要

哺乳动物的睾丸有两个主要功能,即产生配子以进行繁殖,以及合成类固醇和肽类激素以促进雄性化。这些过程受到严格调控,涉及许多生殖细胞和体细胞类型之间的复杂相互作用,这些细胞构成了一个独特的微环境,称为生殖干细胞龛。在人类中,正常睾丸发育或功能的失败与多种男性生殖障碍有关,包括性发育障碍、不育和睾丸癌。虽然啮齿动物模型的研究提供了对调节睾丸的信号通路和分子机制的详细了解,但睾丸发育、功能和生殖障碍方面存在重要的物种差异,这突出表明需要利用人类睾丸组织或细胞的合适实验模型。在这篇综述中,我们概述了用于维持不同发育时间点的人类睾丸组织和细胞的实验方法,并讨论了相关的终点。这些终点包括睾丸内细胞谱系的存活、增殖和分化,以及自分泌、旁分泌和内分泌功能。我们还强调了这些实验方法在模拟环境暴露对睾丸发育和功能的影响方面的应用。

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