Zhao Baohui, Koon Deanna, Curtis Allyson L, Soper Jessica, Bethin Kathleen E
Department of Pediatrics and Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN 46202, USA.
Reprod Biol Endocrinol. 2007 Jul 6;5:28. doi: 10.1186/1477-7827-5-28.
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.
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.
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.
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 transcription factor binding sites that are shared by many of the 9 genes identified here including; estrogen and progesterone response elements and Ets binding sites. In summary, this work identifies 9 uterine murine genes that may play a role in parturition. The function of these genes is consistent with an important role of the immune system in parturition.
早产是所有婴儿死亡的主要原因。2004年，所有出生婴儿中有12.5%为早产。为了理解早产，我们必须首先了解正常分娩。由于小鼠和人类在孕期发生的许多子宫肌层变化相似，且小鼠妊娠期短，我们研究了小鼠孕期子宫中发生变化的基因。在此，我们使用微阵列分析来鉴定妊娠小鼠子宫中在延迟分娩的环氧化酶-1基因敲除小鼠模型中差异调节的基因。
从怀孕的野生型和环氧化酶-1基因敲除小鼠中收集妊娠第18.0天的子宫（n = 4）。部分子宫用于制作冰冻切片，其余部分用于分离RNA。在印第安纳大学医学院基因组核心实验室进行微阵列分析，并使用微阵列数据门户进行分析。进行Northern分析以确认微阵列数据，并通过原位杂交确定这些基因在妊娠子宫中的定位。
我们鉴定出277个在妊娠第18.0天的环氧化酶-1基因敲除小鼠中异常表达的基因。其中9个基因在妊娠后半期的正常小鼠子宫中也受到调节。这些基因中的许多都参与免疫反应，这与免疫系统在分娩中的重要作用一致。通过Northern分析证实，其中4个基因；精氨酸酶I、IgJ、肿瘤坏死因子受体超家族9和肌钙蛋白；在基因敲除小鼠孕期表达失调。这些基因的原位杂交显示在妊娠野生型和Cox-1基因敲除小鼠子宫中的位置相似。
据我们所知，这是首次证明这4个基因在小鼠妊娠晚期子宫中的定位。这里鉴定出的9个基因中有许多共享几个推定的转录因子结合位点，包括；雌激素和孕激素反应元件以及Ets结合位点。总之，这项工作鉴定出9个可能在分娩中起作用的小鼠子宫基因。这些基因的功能与免疫系统在分娩中的重要作用一致。
