Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice

TLDR

Cervical remodeling in pregnancy proceeds through overlapping phases—softening, ripening, dilation/labor, and post‑partum repair. The study aims to uncover the molecular mechanisms underlying cervical remodeling to better understand parturition and preterm labor. Softening begins around gestation days 10–12, preserves tissue strength while increasing collagen solubility, and is marked by upregulation of epithelial mucosal‑protection genes such as Tff1 and Spink5, with no major changes in proliferation, hydration, or inflammatory cell distribution.

Abstract

Cervical remodeling during pregnancy and parturition is a single progressive process that can be loosely divided into four overlapping phases termed softening, ripening, dilation/labor, and post partum repair. Elucidating the molecular mechanisms that facilitate all phases of cervical remodeling is critical for an understanding of parturition and for identifying processes that are misregulated in preterm labor, a significant cause of perinatal morbidity. In the present study, biomechanical measurements indicate that softening was initiated between gestation days 10 and 12 of mouse pregnancy, and in contrast to cervical ripening on day 18, the softened cervix maintains tissue strength. Although preceded by increased collagen solubility, cervical softening is not characterized by significant increases in cell proliferation, tissue hydration or changes in the distribution of inflammatory cells. Gene expression studies reveal a potentially important role of cervical epithelia during softening and ripening in maintenance of an immunomucosal barrier that protects the stromal compartment during matrix remodeling. Expression of two genes involved in repair and protection of the epithelial permeability barrier in the gut (trefoil factor 1) and skin (serine protease inhibitor Kazal type 5) were increased during softening and/or ripening. Another gene whose function remains to be elucidated, purkinje cell protein 4, declines in expression as remodeling progressed. Collectively, these results indicate that cervical softening during pregnancy is a unique phase of the tissue remodeling process characterized by increased collagen solubility, maintenance of tissue strength, and upregulation of genes involved in mucosal protection.