Molecular and Mechanical Investigations to Define Collagen and Elastic Fiber Homeostasis in Cervical Remodeling During a Term and Preterm Pregnancy

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Abstract The remodeling of the cervix to prepare for birth begins early in pregnancy and is orchestrated by a precisely timed change in the structure and mechanical function of the cervical extracellular matrix (ECM). Understanding the molecular pathways that alter the ECM in pregnancy while maintaining a synthesis and degradation equilibrium is necessary to discern cervical function and how it mechanically protects the fetus. More importantly, it is critical to determine when and how these cervical ECM synthesis and degradation processes are perturbed, which compromise cervical mechanical function and creates a risk for preterm birth. Our groups prior work provides evidence 1) of rapid collagen turnover rates in both nonpregnant and pregnant cervix 2) dysfunctional cervical extracellular matrix leads to disrupted cervical biomechanical function in novel mouse models 3) cervical mechanical properties evolve in distinct stages in concert with shifts in ECM structure and 4) mouse models of cervical dysfunction are a useful tool to evaluate cervical mechanics. Building on these findings, we aim to better define molecular pathways of collagen degradation and elastic fiber elastogenesis that ensure ECM homeostasis in physiologic remodeling. Secondly, we aim to understand the complexity of mechanical parameters derived from collagen and elastic fibers at multiple length scales. Collectively, the proposed studies, based on compelling preliminary data, can expand our understanding of basic mechanisms in cervical biology and mechanobiology and expand the possibilities for clinical intervention in PTB.