Schepens Eye Research Institute, Department of Ophthalmology, Boston, Massachusetts 02114, USA.
Invest Ophthalmol Vis Sci. 2013 Feb 5;54(2):987-98. doi: 10.1167/iovs.12-10992.
We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice.
Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays.
Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice.
Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland.
我们假设,控制雌激素生物合成的酶——芳香酶在睑板腺的性别差异中起主要作用。为了开始验证这一假设,我们研究了芳香酶缺失(完全消除雌激素产生)对雄性和雌性小鼠腺基因表达和组织学的影响。
从成年、年龄匹配的野生型(WT)和芳香酶敲除(ArKO)小鼠中获得睑板腺。对组织进行组织学处理或总 RNA 的分离,通过微阵列分析差异表达的 mRNA。
我们的结果表明,芳香酶显著影响睑板腺中超过一千个基因的表达。这种影响的性质主要是性别依赖性的。此外,芳香酶对性别相关基因表达差异的影响主要是基因型特异性的。然而,生物过程、分子功能和细胞成分本体论以及 KEGG(京都基因和基因组百科全书)途径中的许多性别相关变化在 WT 和 ArKO 小鼠之间非常相似。芳香酶活性的丧失对雄性或雌性小鼠的睑板腺组织学没有明显影响。
我们的发现表明,芳香酶对睑板腺的基因表达有显著影响。这种影响的性质是性别依赖性和基因型特异性的;然而,基因本体论和 KEGG 途径中的许多性别相关变化在 WT 和 ArKO 小鼠之间相似。因此,芳香酶,进而雌激素,似乎在小鼠睑板腺的性别差异中不起主要作用。