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人类诱导多能干细胞与男性不育:当前进展与展望概述。

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

机构信息

Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.

Center for Reproductive Medicine, Wuhan Tongji Reproductive Medicine Hospital, 128 Sanyang Road, Wuhan 430013, China.

出版信息

Hum Reprod. 2018 Feb 1;33(2):188-195. doi: 10.1093/humrep/dex369.

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.

摘要

最近,在治疗男性不育症的 ART 方面取得了重大进展。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,大多数夫妇希望拥有自己的遗传相关的孩子。人类诱导多能干细胞(hiPSCs)可以从患者的体细胞中产生,并且从患者特异性 iPSCs 体外衍生功能性生殖细胞可能为不育夫妇提供新的治疗策略。人类原始生殖细胞的总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。与处于原始状态的小鼠 iPSCs(miPSCs)不同,hiPSCs 表现出已启动的多能性,其生殖细胞命运的潜力较小。基于在小鼠中的研究,已经使用不同的方案从 hiPSCs 中衍生出不同阶段的雄性生殖细胞,包括自发分化、生殖细胞调节剂的过表达、细胞因子的添加、与体外性腺细胞共培养和异种移植。本综述的目的是总结从 hiPSCs 中衍生雄性生殖细胞的最新进展,并提出 hiPSCs 在男性不育症的医学应用以及男性生殖细胞发育的基础研究中的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d7/5850345/0977d9140e2a/dex369f01.jpg

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