Department of Human Anatomy and Histology and Embryology, the Fourth Military Medical University, Xi'an, People's Republic of China.
PLoS One. 2010 Nov 3;5(11):e15439. doi: 10.1371/journal.pone.0015439.
Metastasis-associated protein 1 (MTA1), the founding member of the MTA family of genes, can modulate transcription by influencing the status of chromatin remodeling. Despite its strong correlation with the metastatic potential of cancer cells, MTA1 can also regulate crucial cellular pathways by modifying the acetylation status. We have previously reported the presence of MTA1/MTA1 in human and mouse testes, providing the evidence for its involvement in the regulation of testicular function during murine spermatogenesis. The objective of present study was to further assess the localization of MTA1 in mouse epididymis on both transcriptional and translational level, and then to explore whether MTA1 expression is regulated by androgens and postnatal epididymal development.
METHODOLOGY/PRINCIPAL FINDINGS: Mice were deprived of circulating androgen by bilaterally castration and were then supplemented with exogenous testosterone propionate for one week. MTA1 was immunolocalized in the epithelium of the entire epididymis with the maximal expression in the nuclei of principal cells and of clear cells in proximal region. Its expression decreased gradually after castration, whereas testosterone treatment could restore the expression, indicating that the expression of this gene is dependent on androgen. During postnatal development, the protein expression in the epididymis began to appear from day 7 to day 14, increased dramatically from postnatal day 28, and peaked at adulthood onwards, coinciding with both the well differentiated status of epididymis and the mature levels of circulating androgens. This region- and cell-specific pattern was also conservative in normal human epididymis.
Our data suggest that the expression of MTA1 protein could be regulated by androgen pathway and its expression level is closely associated with the postnatal development of the epididymis, giving rise to the possibility that this gene plays a potential role in sperm maturation and fertility.
转移相关蛋白 1（MTA1）是 MTA 家族基因的创始成员，可通过影响染色质重塑状态来调节转录。尽管它与癌细胞的转移潜力密切相关，但 MTA1 还可以通过修饰乙酰化状态来调节关键的细胞途径。我们之前报道了 MTA1/MTA1 存在于人和小鼠的睾丸中，这为其参与调控小鼠精子发生过程中的睾丸功能提供了证据。本研究的目的是进一步评估 MTA1 在小鼠附睾中的转录和翻译水平上的定位，然后探讨 MTA1 的表达是否受雄激素和生后附睾发育的调节。
方法/主要发现：通过双侧去势剥夺小鼠的循环雄激素，然后用外源性丙酸睾酮处理一周。MTA1 在整个附睾上皮中免疫定位，在主细胞和近端透明细胞的核中表达最强。去势后其表达逐渐下降，而睾酮处理可恢复其表达，表明该基因的表达依赖于雄激素。在生后发育过程中，附睾中的蛋白表达从第 7 天开始出现，第 14 天急剧增加，从生后第 28 天开始急剧增加，并在成年期达到高峰，与附睾的高度分化状态和循环雄激素的成熟水平相一致。这种区域和细胞特异性模式在正常人类附睾中也是保守的。
我们的数据表明，MTA1 蛋白的表达可能受雄激素途径调节，其表达水平与附睾的生后发育密切相关，这使得该基因在精子成熟和生育能力中可能发挥潜在作用。
