Influence of Aromatase Absence on the Gene Expression and Histology of the Mouse Meibomian Gland
Influence of Aromatase Absence on the Gene Expression and Histology of the Mouse Meibomian Gland
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DOI：
10.1167/iovs.12-10992
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发表时间：
2013-02-01
影响因子：
4.4
通讯作者：
Sullivan, David A.
中科院分区：
文献类型：
--
作者：
Darabad, Raheleh Rahimi;Suzuki, Tomo;Sullivan, David A.
目的。我们假设芳香酶，一种控制雌激素生物合成的酶，在眉板腺与性别相关的差异中起着主要作用。为了验证这一假说，我们研究了芳香酶的缺失对雄性和雌性小鼠的腺体基因表达和组织学的影响。芳香化酶的缺失完全消除了雌激素的产生。方法：从成年、年龄匹配的野生型(WT)和芳香酶基因敲除(ARKO)小鼠获得眉毛腺。对组织进行组织学处理或提取总RNA，利用微阵列技术分析差异表达的mRNAs。结果芳香化酶显著影响眉板腺中一千多个基因的表达。这种影响的性质主要与性别有关。此外，芳香酶对性别相关的基因表达差异的影响主要是基因型特有的。然而，在WT和ARKO小鼠之间，生物过程、分子功能和细胞组件本体论以及KEGG(京都基因和基因组百科全书)途径中的许多与性别相关的变异都非常相似。芳香化酶活性的丧失对雌雄小鼠眉毛腺的组织学无明显影响。结论我们的研究结果表明，芳香化酶对眉毛腺的基因表达有显著影响。这种影响的性质是性别相关的，也是特定于基因型的；然而，在WT和ARKO小鼠之间，基因本体论和KEGG途径中的许多性别相关变异是相似的。因此，似乎芳香酶和雌激素在小鼠眉毛腺的性别差异中并不起主要作用。(投资眼科VS科学。2013年；54：987-998)doi：10.1167/iovs.12-10992
PURPOSE. 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.METHODS. 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.RESULTS. 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.CONCLUSIONS. 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. (Invest Ophthalmol Vis Sci. 2013;54:987-998) DOI:10.1167/iovs.12-10992