Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxyg

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BioMed Central

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Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse Baohui Zhao, Deanna Koon, Allyson L Curtis, Jessica Soper and Kathleen E Bethin* Address: Department of Pediatrics and Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN 46202, USA Email: Baohui Zhao - [email protected]; Deanna Koon - [email protected]; Allyson L Curtis - [email protected]; Jessica Soper - [email protected]; Kathleen E Bethin* - [email protected] * Corresponding author

Published: 6 July 2007 Reproductive Biology and Endocrinology 2007, 5:28

doi:10.1186/1477-7827-5-28

Received: 11 May 2007 Accepted: 6 July 2007

This article is available from: http://www.rbej.com/content/5/1/28 © 2007 Zhao et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition. Methods: Gestational d18.0 uteri (n = 4) were collected from pregnant wild-type and cyclooxygenase-1 knockout mice. Part of the uterus was used for frozen sections and RNA was isolated from the remainder. Microarray analysis was performed at the Indiana University School of Medicine Genomic Core and analyzed using the Microarray Data Portal. Northern analysis was performed to confirm microarray data and the genes localized in the gravid uterus by in situ hybridization. Results: We identified 277 genes that are abnormally expressed in the gravid d18.0 cyclooxygenase-1 knockout mouse. Nine of these genes are also regulated in the normal murine uterus during the last half of gestation. Many of these genes are involved in the immune response, consistent with an important role of the immune system in parturition. Expression of 4 of these genes; arginase I, IgJ, Tnfrsf9 and troponin; was confirmed by Northern analysis to be mis-regulated during pregnancy in the knockout mouse. In situ hybridization of these genes demonstrated a similar location in the gravid wild-type and Cox-1 knockout mouse uteri. Conclusion: To our knowledge, this is the first work to demonstrate the uterine location of these 4 genes in the mouse during late pregnancy. There are several putative