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我们能否培育精子?基于当前动物和人类精子发生模型的转化视角。

Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models.

机构信息

Department of Surgery, University of Toronto, Toronto, Ont., Canada.

出版信息

Asian J Androl. 2011 Sep;13(5):677-82. doi: 10.1038/aja.2011.88. Epub 2011 Jul 18.

DOI:10.1038/aja.2011.88
PMID:21765440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3752530/
Abstract

There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elude andrologists. Having the ability to 'grow' human sperm would be a tremendous advance in reproductive biology with multiple possible clinical applications, such as a treatment option for men with testicular failure and azoospermia of multiple etiologies. To understand the complexities of human spermatogenesis in a research environment, model systems have been designed with the intent to replicate the testicular microenvironment. Currently, there are both in vivo and in vitro model systems. In vivo model systems involve the transplantation of either spermatogonial stem cells or testicular xenographs. In vitro model systems involve the use of pluripotent stem cells and complex coculturing and/or three-dimensional culturing techniques. This review discusses the basic methodologies, possible clinical applications, benefits and limitations of each model system. Although these model systems have greatly improved our understanding of human spermatogenesis, we unfortunately have not been successful in demonstrating complete human spermatogenesis outside of the testicle.

摘要

在男性因素不孕的诊断和治疗方面已经取得了巨大的进展;然而,负责在睾丸环境之外重建精子发生的机制仍然让男科医生感到困惑。能够“培育”人类精子将是生殖生物学的巨大进步,具有多种可能的临床应用,例如为睾丸衰竭和多种病因导致的无精子症的男性提供治疗选择。为了在研究环境中理解人类精子发生的复杂性,设计了模型系统来复制睾丸微环境。目前,有体内和体外模型系统。体内模型系统涉及精原干细胞或睾丸异种移植物的移植。体外模型系统涉及多能干细胞和复杂的共培养和/或三维培养技术的应用。本文综述了每种模型系统的基本方法学、可能的临床应用、优点和局限性。尽管这些模型系统极大地提高了我们对人类精子发生的理解,但不幸的是,我们尚未成功在睾丸外展示完全的人类精子发生。

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2
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引用本文的文献

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Can we induce spermatogenesis in the domestic cat using an in vitro tissue culture approach?我们能否采用体外组织培养方法在家猫体内诱导精子发生?
PLoS One. 2018 Feb 7;13(2):e0191912. doi: 10.1371/journal.pone.0191912. eCollection 2018.

本文引用的文献

1
In vitro production of functional sperm in cultured neonatal mouse testes.体外培养新生鼠睾丸中功能性精子的生成。
Nature. 2011 Mar 24;471(7339):504-7. doi: 10.1038/nature09850.
2
Copy number variation and selection during reprogramming to pluripotency.重编程为多能性过程中的拷贝数变异和选择。
Nature. 2011 Mar 3;471(7336):58-62. doi: 10.1038/nature09871.
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Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.人类诱导多能干细胞中异常表观基因组重编程的热点。
Nature. 2011 Mar 3;471(7336):68-73. doi: 10.1038/nature09798. Epub 2011 Feb 2.
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Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture.在重编程和培养过程中,人类胚胎干细胞和诱导多能干细胞中多能性和细胞增殖基因拷贝数的动态变化。
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5
Nuclear reprogramming to a pluripotent state by three approaches.三种方法实现细胞核重编程为多能性状态。
Nature. 2010 Jun 10;465(7299):704-12. doi: 10.1038/nature09229.
6
Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation.从婴儿供体中移植睾丸组织会导致睾丸加速成熟。
Hum Reprod. 2010 May;25(5):1113-22. doi: 10.1093/humrep/deq001. Epub 2010 Feb 19.
7
Egg-citing advances in generating primordial germ cells in the laboratory.实验室中生成原始生殖细胞的惊人进展。
Biol Reprod. 2010 Feb;82(2):233-4. doi: 10.1095/biolreprod.109.082388. Epub 2009 Dec 16.
8
Propagation of human spermatogonial stem cells in vitro.人精原干细胞的体外增殖
JAMA. 2009 Nov 18;302(19):2127-34. doi: 10.1001/jama.2009.1689.
9
New horizons for in vitro spermatogenesis? An update on novel three-dimensional culture systems as tools for meiotic and post-meiotic differentiation of testicular germ cells.体外精子发生的新视野?新型三维培养系统作为睾丸生殖细胞减数分裂和减数分裂后分化工具的最新进展。
Mol Hum Reprod. 2009 Sep;15(9):521-9. doi: 10.1093/molehr/gap052. Epub 2009 Jun 27.
10
Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by coculture with human fetal gonadal cells.通过与人类胎儿性腺细胞共培养,从人类胚胎干细胞和诱导多能干细胞中衍生原始生殖细胞的效率得到显著提高。
Stem Cells. 2009 Apr;27(4):783-95. doi: 10.1002/stem.13.