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Quantitative evaluation of collagen crosslinks and corresponding tensile mechanical properties in mouse cervical tissue during normal pregnancy.

Yoshida K, Jiang H, Kim M, Vink J, Cremers S, Paik D, Wapner R, Mahendroo M, Myers K - PLoS ONE (2014)

Bottom Line: The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery.Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS).All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Columbia University, New York, New York, United States of America.

ABSTRACT
The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31-0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15.

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Cervix mechanical stiffness and strength decreases with advancing gestation.A) Representative cervical opening vs stress curves for normal cervix with progressing gestation and postpartum with each color representing each gestation day group. Legend: NP - blue, d6 - green, d12 - cyan, d15- magenta, d18 - black, PP - red; n = 3 for each group. B) Table of mechanical properties calculated from mechanical tests with average values  standard deviation. * and ** represents statically significant difference compared to NP and d6 respectively. †represents statically significant difference compared to all other groups.
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pone-0112391-g002: Cervix mechanical stiffness and strength decreases with advancing gestation.A) Representative cervical opening vs stress curves for normal cervix with progressing gestation and postpartum with each color representing each gestation day group. Legend: NP - blue, d6 - green, d12 - cyan, d15- magenta, d18 - black, PP - red; n = 3 for each group. B) Table of mechanical properties calculated from mechanical tests with average values standard deviation. * and ** represents statically significant difference compared to NP and d6 respectively. †represents statically significant difference compared to all other groups.

Mentions: The tensile mechanical response of the cervix changed drastically from a stiff structure into a soft structure as pregnancy progressed (Fig. 2A), which is consistent with previous studies [8]. On average, initial stiffness (slope of the line fit to the initial linear region of loading curve) decreased gradually without significant difference between groups. The final stiffness (slope of the line fit to the linear region of the loading curve before breaking) and the ultimate stress (maximum stress sustained by the tissue before breaking) increased significantly from NP to d6, decreased significantly from d6 to d12 and continued to decrease until d18 (Fig. 2).


Quantitative evaluation of collagen crosslinks and corresponding tensile mechanical properties in mouse cervical tissue during normal pregnancy.

Yoshida K, Jiang H, Kim M, Vink J, Cremers S, Paik D, Wapner R, Mahendroo M, Myers K - PLoS ONE (2014)

Cervix mechanical stiffness and strength decreases with advancing gestation.A) Representative cervical opening vs stress curves for normal cervix with progressing gestation and postpartum with each color representing each gestation day group. Legend: NP - blue, d6 - green, d12 - cyan, d15- magenta, d18 - black, PP - red; n = 3 for each group. B) Table of mechanical properties calculated from mechanical tests with average values  standard deviation. * and ** represents statically significant difference compared to NP and d6 respectively. †represents statically significant difference compared to all other groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232411&req=5

pone-0112391-g002: Cervix mechanical stiffness and strength decreases with advancing gestation.A) Representative cervical opening vs stress curves for normal cervix with progressing gestation and postpartum with each color representing each gestation day group. Legend: NP - blue, d6 - green, d12 - cyan, d15- magenta, d18 - black, PP - red; n = 3 for each group. B) Table of mechanical properties calculated from mechanical tests with average values standard deviation. * and ** represents statically significant difference compared to NP and d6 respectively. †represents statically significant difference compared to all other groups.
Mentions: The tensile mechanical response of the cervix changed drastically from a stiff structure into a soft structure as pregnancy progressed (Fig. 2A), which is consistent with previous studies [8]. On average, initial stiffness (slope of the line fit to the initial linear region of loading curve) decreased gradually without significant difference between groups. The final stiffness (slope of the line fit to the linear region of the loading curve before breaking) and the ultimate stress (maximum stress sustained by the tissue before breaking) increased significantly from NP to d6, decreased significantly from d6 to d12 and continued to decrease until d18 (Fig. 2).

Bottom Line: The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery.Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS).All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Columbia University, New York, New York, United States of America.

ABSTRACT
The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31-0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15.

Show MeSH
Related in: MedlinePlus