目前約有13％ ~ 18％的夫妻被不孕症所困擾，而在這些不孕症患者中，約有一半的病例是由男方的因素所引起。造成男性不孕症的因素目前了解的並不多，主要的異常大部分是發生在精細胞形成過程與精子形成過程。精細胞形成與精子形成是個極其複雜之發育過程，此發育過程是由雙套的生殖細胞經由高度型態上的分化後而形成單套的成熟精子，而這個造精過程也必須要有一些在特定時期才表現的基因參與其中才能完成。
為了找出涉及人類造精過程的眾多基因，我們由造精功能缺陷的病人身上取得一些睪丸組織，再利用這些睪丸組織製造出c-DNA微矩陣晶片，並且分析其基因表現情況。我們發現有一些基因在這些不孕的病人身上其表現量是顯著性的減少。而其中一個即是睪丸專一性溴區段基因，簡稱為BRDT。BRDT蛋白擁有二個bromodomain、一個ET domain和一段PEST序列，且隸屬於BET家族的其中一員。我們初步發現Brdt專一性地表現在睪丸中，再進一步實驗則發現Brdt專一性地表現在生殖細胞中，且其mRNA從粗絲期精母細胞開始被轉錄出來並一直留存在整個精子形成過程中。然而，Brdt蛋白卻表現在較為後期的圓形精細胞到成熟的精子，這種表現情況使我們認為BRDT在精子形成過程中可能參與了某些基因的發育調控。
在精細胞完成減數分裂後之成熟作用而形成精子的這一段期間，染色絲結構會歷經重整作用，此重整作用會使組織蛋白被過渡蛋白1和過渡蛋白2置換掉，接著2種過渡蛋白又會接續被魚精蛋白1和魚精蛋白2所取代。而在早期長形精細胞內，當組織蛋白要被過渡蛋白替換掉的前一刻，組織蛋白會呈現廣範圍的高度乙醯基化，且我們也發現睪丸內的Brdt對於高度乙醯基化的組織蛋白4會產生一些交互作用，另外BRDT在游動力差的人類精子中其表現情況也會下降。因此，我們推論在精子形成過程中，Brdt和高度乙醯基化的組織蛋白之交互作用會調解染色絲的重整作用，若改變此交互作用有可能造成僅有少量的魚精蛋白併入到成熟精子中的染色絲而導致精子的品質變差，再進一步造成受孕能力低弱。我們的研究將會對人類精子發育過程的錯誤提供更深入的了解。

It is estimated that 13-18% of couples are infertile and male factors account for about half of the cases. The causes of male infertility are largely unknown. Of male-factor infertility, defects in spermatogenesis or spermiogenesis account for the majority of cases. Spermatogenesis and spermiogenesis are complex developmental processes. The development of diploid germ cells to morphologically highly differentiated haploid spermatozoa requires stages–specific expression of genes involved in spermatogenesis.
To identify genes which are involved in human spermatogenesis, we studied global gene expression patterns in testicular tissues of men with spermatogenic defect by c-DNA microarrays. We found some genes are significantly down-regulated in infertile men. One of these genes was bromodomain testis-specific gene (BRDT). The BRDT is a member of bromodomain protein with extra terminal domain (BET) family. The BRDT encode protein with a PEST sequence, one ET domain and two copies of a bromodomain. We found that Brdt is exclusively expressed in the testis. Further studies showed that Brdt was exclusively expressed in germ cells. The Brdt transcript started to be detectable in pachytene spermatocytes and persisted throughout spermiogenesis stage. However, Brdt protein is expressed from round spermatid to spermatozoa. The expression pattern suggests that BRDT may be involved in developmental regulation of genes during spermiogenesis.
During the post-meiotic maturation of spermatids into sperm, the chromatin structure undergoes re-organization then core histones are replaced by transition protein-1 and -2, followed by protamine-1 and protamine-2. Immediately before core histones are displacement by transition proteins, the histones are shown to be globally hyperacetylated in early elongating spermatids. We found Brdt interacts with hyperacetylation histone H4 in vivo. Meanwhile, the protein level of Brdt is reduced in pool-motility sperm. It is proposed that interaction between Brdt and hyperacetylated histone may mediate nuclear reorganization in spermiogenesis. Alteration of this interaction may lead to reduced incorporation of protamines into sperm genome and poor-quality sperm. Our study provides further insight into potential developmental errors which may occur during human spermiogenesis.

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