Biaxial contractility, passive biomechanics, and murine cervical remodeling
Preterm birth (PTB) is a global health concern linked to lifelong health conditions in the mother and child. The etiology of PTB is multifactorial and exact pathways of PTB difficult to elucidate. Cervical insufficiency (CI) is a form of spontaneous PTB in which the cervix dilates in early- to mid-pregnancy without uterine contractions. CI remains difficult to diagnose and treat due to a lack of research into cervical function. During early-pregnancy the cervix must remain stiff to maintain the fetus within the uterus, however, in late-pregnancy the cervix must soften and dilate to allow for the passage of the fetus into the vaginal canal. To accomplish both roles, the cervical extracellular matrix (ECM) remodels during pregnancy. A disruption to the normal remodeling process such as accelerated degeneration of ECM proteins may lead to failure of cervical function. In addition to ECM, cervical smooth muscle cells (cSMCs) work to maintain cervical integrity and assist in physiologic processes such as fertilization and labor. Quantification of microstructural content and mechanical testing permits determination of relationships between ECM, cSMC, and cervical function. Past research quantified microstructural, mechanical, and contractile properties of the cervix; however, mechanical testing and contractility protocols were uniaxial. Uniaxial testing requires disruptive specimen preparation and investigates circumferential and axial properties independently. The cervix, however, is loaded multiaxially in vivo and is anisotropic. Towards this end, biaxial inflation-extension testing of the cervix overcomes these limitations by enabling simultaneous assessment of circumferential and longitudinal mechanical properties and contractility. Determining mechanical properties, contractility, and microstructure of the cervix in the nulliparous and parous state enables the development of computational models of cervical remodeling to better understand the etiology of CI. Therefore, this study sought to characterize cervical remodeling by determining the evolving biaxial mechanical properties, contractility, and microstructural composition of the nulliparous and parous murine cervix.