Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Biol Reprod. 2009 Dec;81(6):1226-32. doi: 10.1095/biolreprod.108.075309. Epub 2009 Aug 14.
Premature cervical ripening is believed to contribute to preterm birth (PTB). Preterm cervical ripening may be due to an aberrant regulation in timing of the same processes that occur at term, or may result from unique molecular mechanisms. Using mouse models of PTB, this study sought to investigate if the molecular mechanisms that govern cervical ripening were similar between preterm and term. Lipopolysaccharide (LPS) is infused into the uterine horn to create a mouse model of inflammation-induced PTB. For a noninfectious model of PTB, RU486 was administered. Both models result in delivery of pups in 8-24 h. Cervical tissues were collected from these models, as well as throughout gestation. Cervical tissues from E15 (preterm), E15 LPS (preterm inflammation), and E18.5 (term) were used for microarray analysis (n = 18). Additional experiments using gestational time course specimens were performed to confirm microarray results. Specific gene pathways were differentially expressed between the groups. Genes involved in immunity and inflammation were increased in the cervix in inflammation-induced PTB; term labor was not associated with differential expression of immune pathways. Cytokine expression was not increased in cervices during term labor, but was increased in the pospartum period. Epithelial cell differentiation pathway was significantly altered in term, but not preterm, labor. Activation of immune pathways may be sufficient for cervical ripening, but does not appear necessary. Differential expression of the epithelial cell differentiation pathway appears necessary in the process of cervical repair. Our results indicate that the molecular mechanisms governing preterm and term cervical ripening are distinctly different.
早产宫颈成熟被认为会导致早产 (PTB)。早产宫颈成熟可能是由于在足月时发生的相同过程的时间调节异常，也可能是由于独特的分子机制引起的。本研究使用早产小鼠模型，旨在研究控制宫颈成熟的分子机制在早产和足月之间是否相似。将脂多糖 (LPS) 注入子宫角以创建 LPS 诱导的 PTB 小鼠模型。对于非感染性 PTB 模型，给予 RU486。这两种模型都会导致在 8-24 小时内分娩幼崽。从这些模型以及整个妊娠期收集宫颈组织。来自 E15（早产）、E15 LPS（早产炎症）和 E18.5（足月）的宫颈组织用于微阵列分析 (n = 18)。还进行了使用妊娠时间过程标本的额外实验以验证微阵列结果。特定基因途径在各组之间存在差异表达。在炎症诱导的 PTB 中，宫颈中参与免疫和炎症的基因增加；足月分娩与免疫途径的差异表达无关。在足月分娩期间，细胞因子表达没有增加，但在产后期间增加。上皮细胞分化途径在足月时明显改变，但在早产时没有改变。免疫途径的激活可能足以使宫颈成熟，但似乎不是必需的。上皮细胞分化途径的差异表达似乎是宫颈修复过程中必需的。我们的结果表明，控制早产和足月宫颈成熟的分子机制明显不同。
