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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February 2014
Research-Article
Cervical Collagen Network Remodeling in Normal Pregnancy and Disrupted Parturition in Antxr2 Deficient Mice
Kyoko Yoshida,
Kyoko Yoshida
Graduate Research Assistant
Department of Mechanical Engineering,
e-mail: ky2218@columbia.edu
Department of Mechanical Engineering,
Columbia University
,New York, NY 10027
e-mail: ky2218@columbia.edu
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Joy Vink,
Joy Vink
Assistant Clinical Professor
Department of Obstetrics and Gynecology,
e-mail: jyv2101@mail.cumc.columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: jyv2101@mail.cumc.columbia.edu
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Jan Kitajewski,
Jan Kitajewski
Charles and Marie Robertson Professor
Department of Obstetrics and Gynecology,
e-mail: jkk9@columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: jkk9@columbia.edu
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Ronald Wapner,
Ronald Wapner
Vice Chairman for Research
Department of Obstetrics and Gynecology,
e-mail: rw2191@mail.cumc.columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: rw2191@mail.cumc.columbia.edu
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Hongfeng Jiang,
Hongfeng Jiang
Associate Research Scientist
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
e-mail: hj2238@mail.cumc.columbia.edu
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
Columbia University Medical Center
,New York, NY 10032
e-mail: hj2238@mail.cumc.columbia.edu
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Serge Cremers,
Serge Cremers
Assistant Professor of Medical Sciences
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
e-mail: sc2752@mail.cumc.columbia.edu
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
Columbia University Medical Center
,New York, NY 10032
e-mail: sc2752@mail.cumc.columbia.edu
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Kristin Myers
Kristin Myers
Assistant Professor
Department of Mechanical Engineering,
e-mail: kmm2233@columbia.edu
Department of Mechanical Engineering,
Columbia University
, New York, NY 10027
e-mail: kmm2233@columbia.edu
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Kyoko Yoshida
Graduate Research Assistant
Department of Mechanical Engineering,
e-mail: ky2218@columbia.edu
Department of Mechanical Engineering,
Columbia University
,New York, NY 10027
e-mail: ky2218@columbia.edu
Claire Reeves
Joy Vink
Assistant Clinical Professor
Department of Obstetrics and Gynecology,
e-mail: jyv2101@mail.cumc.columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: jyv2101@mail.cumc.columbia.edu
Jan Kitajewski
Charles and Marie Robertson Professor
Department of Obstetrics and Gynecology,
e-mail: jkk9@columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: jkk9@columbia.edu
Ronald Wapner
Vice Chairman for Research
Department of Obstetrics and Gynecology,
e-mail: rw2191@mail.cumc.columbia.edu
Department of Obstetrics and Gynecology,
Columbia University Medical Center
,New York, NY 10032
e-mail: rw2191@mail.cumc.columbia.edu
Hongfeng Jiang
Associate Research Scientist
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
e-mail: hj2238@mail.cumc.columbia.edu
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
Columbia University Medical Center
,New York, NY 10032
e-mail: hj2238@mail.cumc.columbia.edu
Serge Cremers
Assistant Professor of Medical Sciences
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
e-mail: sc2752@mail.cumc.columbia.edu
Irving Institute for Clinical
and Translational Research,
Department of Medicine,
Columbia University Medical Center
,New York, NY 10032
e-mail: sc2752@mail.cumc.columbia.edu
Kristin Myers
Assistant Professor
Department of Mechanical Engineering,
e-mail: kmm2233@columbia.edu
Department of Mechanical Engineering,
Columbia University
, New York, NY 10027
e-mail: kmm2233@columbia.edu
Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received September 5, 2013; final manuscript received December 18, 2013; accepted manuscript posted January 6, 2014; published online February 5, 2014. Editor: Beth Winkelstein.
J Biomech Eng. Feb 2014, 136(2): 021017 (8 pages)
Published Online: February 5, 2014
Article history
Received:
September 5, 2013
Revision Received:
December 18, 2013
Accepted:
January 6, 2014
Citation
Yoshida, K., Reeves, C., Vink, J., Kitajewski, J., Wapner, R., Jiang, H., Cremers, S., and Myers, K. (February 5, 2014). "Cervical Collagen Network Remodeling in Normal Pregnancy and Disrupted Parturition in Antxr2 Deficient Mice." ASME. J Biomech Eng. February 2014; 136(2): 021017. https://doi.org/10.1115/1.4026423
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