Molecular mechanisms of postnatal differentiation of epididymis regulated by sex hormones

附睾在形态上可分为头部、体部和尾部三个区域，各区域有其特定的管腔环境。本研究通过检测小鼠生后发育过程中附睾基因的表达，探讨附睾区域功能分化的分子机制。基因芯片分析表明，基因表达模式在出生后3周内发生显著变化，3周龄时达到成年模式。这些基因在头、体、尾三个区域的表达差异较大。接下来，将雄性新生小鼠暴露于己烯雌酚（一种合成雌激素），以研究性激素如何影响产后附睾发育。该处理导致附睾相对间质过度生长和I型胶原基因（col 1a 1和col 1a 2）的高表达。原位杂交分析表明，基质细胞的相对过度生长是由于col 1a 1和col 1a 2基因表达增加所致。此外，通过基因芯片和实时荧光定量PCR分析，还鉴定了一个新基因（Serpina 1f）和4个未知的小鼠附睾特异性基因（Lcp 1、Cuzd 1、Teddm 1和Wfdc 16）。这些基因的表达在幼鱼期迅速增加。本研究还分析了它们的表达区域以及性激素对这些基因表达的调控。实时荧光定量RT-PCR分析水通道蛋白（AQP）的基因表达。结果发现，小鼠附睾中有10种水通道蛋白（AQP 1 -9和AQP 11）的表达，其中许多AQP的表达在雌激素过量时降低。

Epididymis is morphologically divided into the caput, corpus and cauda regions, which have their own specific luminal environments. In this study, gene expression in the mouse epididymis was examined during postnatal development to analyze molecular mechanisms of functional differentiation of epididymal regions. DNA microarray analysis revealed that gene expression pattern remarkably changes during postnatal three weeks and reach to the adult pattern by 3 weeks of age. These gene expressions were quite different among the caput, corpus and cauda regions. Next, male newborn mice were exposed to diethylstilbestrol, a synthetic estrogen, to examine how sex hormones affect the postnatal development of epididymis. This treatment caused relative stromal overgrowth of epididymis and high expression of type I collagen genes (col1a1 and col1a2). It was revealed by in situ hybridization analysis that the relative stromal overgrowth is caused by increase in expression of col1a1 and col1a2 genes in each stromal cell. Further, a novel gene (Serpina1f) and 4 unknown mouse epididymis-specific genes (Lcp1, Cuzd1, Teddm1 and Wfdc16) were identified by DNA microarray and real-time RT-PCR analyses. The expression of these genes was confirmed to increase rapidly during juvenile period. Their expression areas and regulation of expression of these genes by sex hormones were also analyzed in this study. Gene expression of aquaporins (AQPs), water channel proteins, was also analyzed by real-time RT-PCR. It was found that 10 types of AQP (AQP1-9 and 11) express in mouse epididymis and expression of many of AQPs decrease by excess of estrogens.