The Molecular Mechanisms of Cervical Ripening Differ between Term and Preterm Birth

TLDR

The study compares mechanisms of premature cervical ripening in mouse models of infection‑ or progesterone‑withdrawal‑induced preterm birth with term cervical ripening. The authors assessed cervical tissue morphology, weight, gene expression, collagen content, and immune cell populations. Premature ripening induced by mifepristone accelerates term‑ripening processes and partially activates pro‑inflammatory and immunosuppressive pathways, whereas infection‑induced ripening is driven by neutrophil influx, a robust pro‑inflammatory response, and upregulation of prostaglandin‑synthesizing enzymes, demonstrating that cervical ripening can be initiated by distinct mechanisms and informing targeted preterm‑birth therapies.

Abstract

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.