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Changes in global gene expression in rat myometrium in transition from late pregnancy to parturition

¹ Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
² Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
⁴ Department of Physiology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
³ Brain Research Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California

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 (100-fold by microarray and 50-fold by real-time PCR). The emerging profile highlights biochemical cascades occurring in a period of 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.

smooth muscle; microarray; labor; aquaporin; gene regulation