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Research Papers

Cervical Collagen Network Remodeling in Normal Pregnancy and Disrupted Parturition in Antxr2 Deficient Mice

[+] Author and Article Information
Kyoko Yoshida

Graduate Research Assistant
Department of Mechanical Engineering,
Columbia University,
New York, NY 10027
e-mail: ky2218@columbia.edu

Claire Reeves

Associate Managing Editor
BioScience Writers, LLC,
Houston, TX 77025
e-mail: creeves2002@gmail.com

Joy Vink

Assistant Clinical Professor
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,
Columbia University Medical Center,
New York, NY 10032
e-mail: jkk9@columbia.edu

Ronald Wapner

Vice Chairman for Research
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,
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,
Columbia University Medical Center,
New York, NY 10032
e-mail: sc2752@mail.cumc.columbia.edu

Kristin Myers

Assistant Professor
Department of Mechanical Engineering,
Columbia University, New York, NY 10027
e-mail: kmm2233@columbia.edu

See http://www.febio.org.

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 136(2), 021017 (Feb 05, 2014) (8 pages) Paper No: BIO-13-1411; doi: 10.1115/1.4026423 History: Received September 05, 2013; Revised December 18, 2013; Accepted January 06, 2014

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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Figures

Grahic Jump Location
Fig. 1

(a) Experimental setup for osmotic loading tests with the camera setup. Camera images of (b) the internal os (the uterine side of the cervix), and (c) along the length of the cervix sample with the dimensions taken using the VIC-2D.

Grahic Jump Location
Fig. 2

Equilibrium swelling volume with best fit FEA lines: N = 3 for all sample groups; and * indicates the statistical significance for Antxr2+/+D18 compared to all other groups (p < 0.05)

Grahic Jump Location
Fig. 3

Ratio of pyridinoline content per collagen content (n = 7 to 9): * indicates the statistical significance between bracketed groups (p < 0.05)

Grahic Jump Location
Fig. 4

Relative equilibrium swelling volume at 300 mOsm NaCl versus collagen crosslink density. A shift from the lower right hand corner to the upper left hand corner indicates active cervical remodeling, indicated by a decrease in collagen crosslink density with an increase in swelling volume. The Antxr2+/+ specimens exhibited active remodeling, whereas the Antxr2-/- specimens did not.

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