Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives.

Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives.
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人类诱导多能干细胞与男性不育:当前进展和前景概述

DOI:
10.1093/humrep/dex369
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发表时间:
2018-02-01
期刊:
Human reproduction (Oxford, England)
影响因子:
--
通讯作者:
Xiong C
Xiong C
中科院分区:
其他
文献类型:
--
作者:
Fang F;Li Z;Zhao Q;Li H;Xiong C

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摘要近年来,ART治疗男性不育症取得了显著进展。然而,目前的ART未能帮助非梗阻性无精子症的不育患者,除非使用供体精子。事实上,大多数夫妇都希望有自己的基因相关的孩子。人类诱导多能干细胞(hiPSC)可以从患者的体细胞产生,并且从患者特异性iPSC体外衍生功能性生殖细胞可以为不育夫妇提供新的治疗策略。人类原始生殖细胞的整体发育动力学与小鼠相似,但越来越多的证据表明,人类和小鼠PGC特化之间存在关键差异。与幼稚状态的小鼠iPSC(miPSC)不同,hiPSC表现出引发的多能性,其具有较低的生殖细胞命运潜力。基于在小鼠中的研究,不同阶段的雄性生殖细胞已经通过不同的方案从hiPSC衍生,包括自发分化、生殖细胞调节因子的过表达、细胞因子的添加、与性腺细胞的体外共培养和异种移植。本文综述了hiPSCs体外诱导分化为男性生殖细胞的研究进展,并展望了hiPSCs在男性不育症治疗和男性生殖细胞发育基础研究中的应用前景。
Abstract Recently, significant progress has been made in ART for the treatment of male infertility. However, current ART has failed to help infertile patients with non-obstructive azoospermia, unless donor sperm is used. In fact, most couples wish to have their own genetically related child. Human induced pluripotent stem cells (hiPSCs) can be generated from patients’ somatic cells and in vitro derivation of functional germ cells from patient-specific iPSCs may provide new therapeutic strategies for infertile couples. The overall developmental dynamics of human primordial germ cells are similar to that in mice, but accumulating evidence suggests that there are crucial differences between human and mouse PGC specification. Unlike mouse iPSCs (miPSCs) in naive state, hiPSCs exhibit a primed pluripotency which possess less potential for the germ cell fate. Based on research in mice, male germ cells at different stages have been derived from hiPSCs with different protocols, including spontaneous differentiation, overexpression of germ cell regulators, addition of cytokines, co-culture with gonadal cells in vitro and xeno-transplantation. The aim of this review is to summarize the current advances in derivation of male germ cells from hiPSCs and raise the perspectives of hiPSCs in medical application for male infertility, as well as in basic research for male germ cell development.
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