Helguera Gustavo, Eghbali Mansoureh, Sforza Daniel, Minosyan Tamara Y, Toro Ligia, Stefani Enrico
Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095-7115, USA.
Physiol Genomics. 2009 Jan 8;36(2):89-97. doi: 10.1152/physiolgenomics.00290.2007. Epub 2008 Nov 11.
The process of parturition involves the complex interplay of factors that change the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery, using high-density DNA microarray. Of 8,740 sequences available in the array, a total of 3,782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term, including connexin 43 and 26, cyclooxygenase 2, and oxytocin receptor, as well as novel genes that have been not previously associated with parturition. Quantitative real-time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of the aquaporin water channel family, was dramatically downregulated during parturition (approximately 100-fold by microarray and approximately 50-fold by real-time PCR). The emerging profile highlights biochemical cascades occurring in a period of approximately 36 h that trigger parturition and the initiation of myometrium reverse remodeling postpartum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipid metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth.
分娩过程涉及多种因素的复杂相互作用,这些因素会改变子宫的兴奋性和收缩活动。我们使用高密度DNA微阵列比较了大鼠分娩前(怀孕21天)和分娩期间子宫肌层的相对基因表达谱。在该阵列中可获得的8740个序列中,总共检测到3782个序列存在。在显著改变的序列中,59个基因上调,82个基因下调。我们能够检测到在足月时表达水平发生改变的基因的变化,包括连接蛋白43和26、环氧化酶2和催产素受体,以及以前与分娩无关的新基因。对选定基因进行的定量实时PCR进一步证实了微阵列数据。在此我们首次报告,水通道蛋白水通道家族的成员水通道蛋白5(AQP5)在分娩期间显著下调(通过微阵列约为100倍,通过实时PCR约为50倍)。新出现的概况突出了在大约36小时内发生的生化级联反应,这些反应引发分娩并启动产后子宫肌层的逆向重塑。微阵列分析揭示了以前怀疑在分娩中起作用的基因。这种调节涉及来自免疫/炎症反应、类固醇/脂质代谢、钙稳态、细胞体积调节、细胞信号传导、细胞分裂和组织重塑的基因,表明在出生过程中存在多种冗余机制发生改变。