Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9032, USA.
Endocrinology. 2011 Mar;152(3):1036-46. doi: 10.1210/en.2010-1105. Epub 2011 Jan 5.
In the current study, the mechanisms of premature cervical ripening in murine models of preterm birth resulting from infection or early progesterone withdrawal were compared with the process of term cervical ripening. Tissue morphology, weight, gene expression, and collagen content along with immune cell populations were evaluated. Premature ripening induced by the progesterone receptor antagonist mifepristone results from an acceleration of processes in place during term ripening as well as partial activation of proinflammatory and immunosuppressive processes observed during postpartum repair. In contrast to term or mifepristone-induced preterm ripening, premature ripening induced in an infection model occurs by a distinct mechanism which is dominated by an influx of neutrophils into the cervix, a robust proinflammatory response and increased expression of prostaglandin-cyclooxygenase-endoperoxide synthase 2, important in prostaglandin biosynthesis. Key findings from this study confirm that cervical ripening can be initiated by more than one mechanism and is not necessarily an acceleration of the physiologic process at term. These results will influence current strategies for identifying specific etiologies of preterm birth and developing subsequent therapies.
在本研究中，比较了感染或早期孕酮撤退引起的早产小鼠模型中早产宫颈成熟的机制与足月宫颈成熟的过程。评估了组织形态、重量、基因表达和胶原含量以及免疫细胞群。孕酮受体拮抗剂米非司酮诱导的早产是由于足月成熟过程中的加速以及产后修复过程中观察到的促炎和免疫抑制过程的部分激活所致。与足月或米非司酮诱导的早产不同，感染模型中诱导的早产是通过一种独特的机制发生的，这种机制主要是中性粒细胞涌入宫颈，强烈的促炎反应和前列腺素-cyclooxygenase-endoperoxide synthase 2 的表达增加，在前列腺素生物合成中很重要。这项研究的主要发现证实，宫颈成熟可以通过多种机制启动，不一定是足月生理过程的加速。这些结果将影响目前用于识别早产特定病因和开发后续治疗方法的策略。
