TY - JOUR
T1 - Cervical collagen network remodeling in normal pregnancy and disrupted parturition in antxr2 deficient mice
AU - Yoshida, Kyoko
AU - Reeves, Claire
AU - Vink, Joy
AU - Kitajewski, Jan
AU - Wapner, Ronald
AU - Jiang, Hongfeng
AU - Cremers, Serge
AU - Myers, Kristin
PY - 2014/2
Y1 - 2014/2
N2 - The remodeling of the cervix from a rigid barrier into a compliant structure, which dilates to allow for delivery, is a critical process for a successful pregnancy. Changes in the mechanical properties of cervical tissue during remodeling are hypothesized to be related to the types of collagen crosslinks within the tissue. To further understand normal and abnormal cervical remodeling, we quantify the material properties and collagen crosslink density of cervical tissue throughout pregnancy from normal wild-type and Anthrax Toxin Receptor 2 knockout (Antxr2-/-) mice. Antxr2-/-females are known to have a parturition defect, in part, due to an excessive accumulation of extracellular matrix proteins in the cervix, particularly collagen. In this study, we determined the mechanical properties in gestation-timed cervical samples by osmotic loading and measured the density of mature collagen crosslink, pyridinoline (PYD), by liquid chromatography tandem mass spectrometry (LC-MSMS). The equilibrium material response of the tissue to loading was investigated using a hyperelastic material model where the stresses in the material are balanced by the osmotic swelling tendencies of the glycosaminoglycans and the tensile restoring forces of a randomly-oriented crosslinked collagen fiber network. This study shows that the swelling response of the cervical tissue increased with decreasing PYD density in normal remodeling. In the Antxr2-/-mice, there was no significant increase in swelling volume or significant decrease in crosslink density with advancing gestation. By comparing the ECM-mechanical response relationships in normal and disrupted parturition mouse models this study shows that a reduction of collagen crosslink density is related to cervical softening and contributes to the cervical remodeling process.
AB - The remodeling of the cervix from a rigid barrier into a compliant structure, which dilates to allow for delivery, is a critical process for a successful pregnancy. Changes in the mechanical properties of cervical tissue during remodeling are hypothesized to be related to the types of collagen crosslinks within the tissue. To further understand normal and abnormal cervical remodeling, we quantify the material properties and collagen crosslink density of cervical tissue throughout pregnancy from normal wild-type and Anthrax Toxin Receptor 2 knockout (Antxr2-/-) mice. Antxr2-/-females are known to have a parturition defect, in part, due to an excessive accumulation of extracellular matrix proteins in the cervix, particularly collagen. In this study, we determined the mechanical properties in gestation-timed cervical samples by osmotic loading and measured the density of mature collagen crosslink, pyridinoline (PYD), by liquid chromatography tandem mass spectrometry (LC-MSMS). The equilibrium material response of the tissue to loading was investigated using a hyperelastic material model where the stresses in the material are balanced by the osmotic swelling tendencies of the glycosaminoglycans and the tensile restoring forces of a randomly-oriented crosslinked collagen fiber network. This study shows that the swelling response of the cervical tissue increased with decreasing PYD density in normal remodeling. In the Antxr2-/-mice, there was no significant increase in swelling volume or significant decrease in crosslink density with advancing gestation. By comparing the ECM-mechanical response relationships in normal and disrupted parturition mouse models this study shows that a reduction of collagen crosslink density is related to cervical softening and contributes to the cervical remodeling process.
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U2 - 10.1115/1.4026423
DO - 10.1115/1.4026423
M3 - Article
C2 - 24390076
AN - SCOPUS:84896803625
SN - 0148-0731
VL - 136
JO - Journal of biomechanical engineering
JF - Journal of biomechanical engineering
IS - 2
M1 - 021017
ER -