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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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Collagen crosslinks increase in early pregnancy and decrease by late gestation, leading to decreased maturity ratios in late pregnancy.Averaged crosslink density (normalized by collagen) measured with UPLC-ESI-MS/MS for all samples for A) total immature crosslink density (HLNL+DHLNL) B) total mature crosslink density (DPD+PYD), C) maturity ratio (total immature crosslink density: total mature crosslink density), and D) collagen content (per dry weight). * and ** represents statically significant difference compared to NP and d6 respectively. (One-way ANOVA ). NP  =  nonpregnant, d6, d12, d15, d18  =  gestation day 6, 12, 15, 18, PP  =  postpartum. Numbers on top or below boxes are median values for each group.
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pone-0112391-g003: Collagen crosslinks increase in early pregnancy and decrease by late gestation, leading to decreased maturity ratios in late pregnancy.Averaged crosslink density (normalized by collagen) measured with UPLC-ESI-MS/MS for all samples for A) total immature crosslink density (HLNL+DHLNL) B) total mature crosslink density (DPD+PYD), C) maturity ratio (total immature crosslink density: total mature crosslink density), and D) collagen content (per dry weight). * and ** represents statically significant difference compared to NP and d6 respectively. (One-way ANOVA ). NP  =  nonpregnant, d6, d12, d15, d18  =  gestation day 6, 12, 15, 18, PP  =  postpartum. Numbers on top or below boxes are median values for each group.

Mentions: Immature crosslinks remained unchanged while mature crosslinks decreased during the early softening stage (d6 to d12 to d15). Total immature crosslink density (HLNL+DHLNL) increased from NP to d6, but not significantly (NP: 0.31 to d6: 0.51) and they decreased between d12 and d15, but not significantly (d12: 0.59 vs d15: 0.36). At d15, d18, and PP the density values (range: 0.36–0.49) were not significantly different from NP levels (0.31) (Fig. 3A). Total mature crosslink density (DPD+PYD) increased from NP to d6, but not significantly (NP: 0.069, d6: 0.17) and decreased significantly from d6 (0.17) to d12 (0.097) to d15 (0.026). Total mature crosslink density levels at d15, and d18 (range: 0.026–0.028) were significantly lower than NP levels (0.069) (Fig. 3B).


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)

Collagen crosslinks increase in early pregnancy and decrease by late gestation, leading to decreased maturity ratios in late pregnancy.Averaged crosslink density (normalized by collagen) measured with UPLC-ESI-MS/MS for all samples for A) total immature crosslink density (HLNL+DHLNL) B) total mature crosslink density (DPD+PYD), C) maturity ratio (total immature crosslink density: total mature crosslink density), and D) collagen content (per dry weight). * and ** represents statically significant difference compared to NP and d6 respectively. (One-way ANOVA ). NP  =  nonpregnant, d6, d12, d15, d18  =  gestation day 6, 12, 15, 18, PP  =  postpartum. Numbers on top or below boxes are median values for each group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112391-g003: Collagen crosslinks increase in early pregnancy and decrease by late gestation, leading to decreased maturity ratios in late pregnancy.Averaged crosslink density (normalized by collagen) measured with UPLC-ESI-MS/MS for all samples for A) total immature crosslink density (HLNL+DHLNL) B) total mature crosslink density (DPD+PYD), C) maturity ratio (total immature crosslink density: total mature crosslink density), and D) collagen content (per dry weight). * and ** represents statically significant difference compared to NP and d6 respectively. (One-way ANOVA ). NP  =  nonpregnant, d6, d12, d15, d18  =  gestation day 6, 12, 15, 18, PP  =  postpartum. Numbers on top or below boxes are median values for each group.
Mentions: Immature crosslinks remained unchanged while mature crosslinks decreased during the early softening stage (d6 to d12 to d15). Total immature crosslink density (HLNL+DHLNL) increased from NP to d6, but not significantly (NP: 0.31 to d6: 0.51) and they decreased between d12 and d15, but not significantly (d12: 0.59 vs d15: 0.36). At d15, d18, and PP the density values (range: 0.36–0.49) were not significantly different from NP levels (0.31) (Fig. 3A). Total mature crosslink density (DPD+PYD) increased from NP to d6, but not significantly (NP: 0.069, d6: 0.17) and decreased significantly from d6 (0.17) to d12 (0.097) to d15 (0.026). Total mature crosslink density levels at d15, and d18 (range: 0.026–0.028) were significantly lower than NP levels (0.069) (Fig. 3B).

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