A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets
A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets
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DOI：
10.1073/pnas.1635054100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Garbers, DL
中科院分区：
文献类型：
--
作者：
Schultz, N;Hamra, FK;Garbers, DL
对哺乳动物精子发育和受精相关事件的了解进展缓慢，部分原因是对所涉及的细胞成分的数量和身份的不确定性。对生殖细胞特异性表达的转录本的测定应该提供一个包括可能的关键蛋白的列表。在本研究中，将在培养中富集于支持细胞或间质细胞的转录本中发现的转录本修剪掉，以产生富集生殖细胞的转录本。对发育中的睾丸中这一谱变化的监测发现，1,652个基因的转录丰度随着减数分裂的开始而显著增加。值得注意的是，其中351个基因（约20%）似乎只在男性生殖系中表达。生殖细胞特异性转录物在睾丸发育早期不太常见。UniGene EST数据库的进一步分析结合定量PCR表明，大约有4%的小鼠基因组专门用于减数分裂后雄性生殖细胞的表达。这些转录物的大多数或许多蛋白质产物可能保留在成熟精子中。有针对性地破坏这些基因中的19个表明，其中大多数对正常生育至关重要。因此，我们发现男性生殖细胞在发育后期特异性表达的基因数量惊人。这个广泛的群体为生殖细胞定向避孕提供了过多的潜在靶点，以及数量惊人的可能对受精至关重要的候选蛋白质。
Understanding mammalian spermatozoan development and the events surrounding fertilization has grown slowly, in part because of uncertainty about the number and identity of the cellular components involved. Determination of those transcripts expressed specifically by germ cells should provide an inclusive list of probable critical proteins. Here, total mouse testis transcript profiles were trimmed of transcripts found in cultures enriched in Sertoli or interstitial cells to yield a germ cell-enriched transcript profile. Monitoring of changes of this profile in the developing testis identified 1,652 genes whose transcript abundance increased markedly coincident with the onset of meiosis. Remarkably, 351 of these genes (approximate to20%) appear to be expressed only in the male germline. Germ cell-specific transcripts are much less common earlier in testis development. Further analysis of the UniGene EST database coupled with quantitative PCR indicates that approximate to4% of the mouse genome is dedicated to expression in postmeiotic male germ cells. Most or many of the protein products of these transcripts are probably retained in mature spermatozoa. Targeted disruption of 19 of these genes has indicated that a majority have roles critical for normal fertility. Thus, we find an astonishing number of genes expressed specifically by male germ cells late in development. This extensive group provides a plethora potential targets for germ cell-directed contraception and a staggering number of candidate proteins that could be critical for fertilization.