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精子发生缺陷导致的男性不育:基因敲除研究的启示

Male infertility caused by spermiogenic defects: lessons from gene knockouts.

作者信息

Yan Wei

机构信息

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

出版信息

Mol Cell Endocrinol. 2009 Jul 10;306(1-2):24-32. doi: 10.1016/j.mce.2009.03.003. Epub 2009 Mar 20.

DOI:10.1016/j.mce.2009.03.003
PMID:19481682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5438260/
Abstract

Spermiogenesis refers to the process by which postmeiotic spermatids differentiate into elongated spermatids and eventually spermatozoa. During spermiogenesis, round spermatids undergo dynamic morphologic changes, which include nuclear condensation and elongation, formation of flagella and acrosome, reorganization of organelles and elimination of cytoplasm upon spermiation. This cellular differentiation process is unique to male haploid germ cells, which may explain why approximately half of the testis-specific genes are exclusively expressed in spermiogenesis. The spermiogenesis-specific expression implies that these genes contribute to either structural or functional aspects of future sperm. Many such genes have been inactivated in mice and some of these gene knockout mice display male infertility due to nonfunctional sperm which display no or various degrees of structural abnormalities. Since the majority of these spermiogenesis-specific genes are highly conserved between mice and humans, findings from knockout mouse studies may be applicable to human infertility. Here, I briefly review some of these spermatid-specific gene knockouts. The mouse studies strongly suggest that sperm quality rather than quantity is a better indicator of male fertility and novel assays should be developed to determine sperm functionality.

摘要

精子形成是指减数分裂后的精子细胞分化为细长型精子细胞并最终形成精子的过程。在精子形成过程中,圆形精子细胞会经历动态的形态变化,包括细胞核浓缩和拉长、鞭毛和顶体的形成、细胞器的重新组织以及精子释放时细胞质的消除。这种细胞分化过程是雄性单倍体生殖细胞所特有的,这或许可以解释为什么大约一半的睾丸特异性基因仅在精子形成过程中表达。精子形成特异性表达意味着这些基因对未来精子的结构或功能方面有贡献。许多这样的基因在小鼠中已被灭活,其中一些基因敲除小鼠由于精子无功能且表现出无或各种程度的结构异常而出现雄性不育。由于这些精子形成特异性基因中的大多数在小鼠和人类之间高度保守,基因敲除小鼠研究的结果可能适用于人类不育症。在此,我简要回顾一些这些精子细胞特异性基因敲除的情况。小鼠研究强烈表明,精子质量而非数量是雄性生育能力的更好指标,应开发新的检测方法来确定精子功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b30/5438260/452d97a0b630/nihms857473f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b30/5438260/310bdefa9e92/nihms857473f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b30/5438260/452d97a0b630/nihms857473f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b30/5438260/310bdefa9e92/nihms857473f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b30/5438260/452d97a0b630/nihms857473f2.jpg

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Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia.SPATA16基因的纯合突变与人类圆头精子症中的男性不育相关。
Am J Hum Genet. 2007 Oct;81(4):813-20. doi: 10.1086/521314. Epub 2007 Aug 21.
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Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility.Spem1的缺失会导致异常的细胞质去除、精子变形和男性不育。
鉴定YBX2和TSKS为睾丸生殖细胞中与STK33相互作用的蛋白。
Reprod Sci. 2025 Mar;32(3):769-782. doi: 10.1007/s43032-025-01798-7. Epub 2025 Feb 5.
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Long-term effects of sub-chronic exposure to L-NAME on reproductive system of male rats.亚慢性暴露于L-精氨酸甲酯对雄性大鼠生殖系统的长期影响。
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5303-5319. doi: 10.1007/s00210-024-03609-3. Epub 2024 Nov 15.
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Adverse Effects of Nicotine on Human Sperm Nuclear Proteins.尼古丁对人类精子核蛋白的不良影响。
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