Genetic background affects the biomechanical behavior of the postpartum mouse cervix.
OBJECTIVE
We hypothesized that the genetic makeup has an impact on the functional behavior of the uterine cervix. Therefore, we compared the biomechanical properties of uterine cervix in postpartum in 2 strains of mice that differ in their underlying regenerative collagen remodeling characteristics: MRL/MpJ+/+ (MRL: high regenerative repair) and C57BL/6 (C57: low regenerative high fibrotic repair).


METHODS
Cervical tensile proprieties were assessed on day 3, 15, and 60 postpartum in MRL (n = 14) and C57 (n = 13) mice (4-5 animals at each time point). Stress-strain curves were generated using Shimadzu EZ-test instrumentation. Cervical tissue was stretched by 0.42 mm/min until rupture. Parameters of viscoelasticity including slope (a measure of stiffness), yield point (YP; moment when tissue changes its proprieties from elastic to plastic), and break point (BP; measure of tissue strength) were recorded and analyzed blindly between strains. Data were normalized to the weight of the tissue and analyzed by 2-way analysis of variance. Histological and collagen birefringence evaluation of the uterine cervix (MRL: n = 4; C57: n = 4) was performed 5 days after delivery.


RESULTS
At 3 and 15 days postpartum, cervices of MRL mice were significantly more compliant than those of C57 (P < .001). MRL mice displayed a significant increase in stiffness from day 3 to day 60 (slope, median +/- SEM: day 3: 3.1 +/- 0.5 vs day 15: 20.3 +/- 4.9 vs day 60: 33.1 +/- 3.5 N/mm per gram; P < .001). In contrast, the stiffness of C57 cervices reached maximum on day 15 (slope day 3: 14.1 +/- 4.3 vs day 15: 40.0 +/- 6.5 N/mm per gram; P = .02) and rested at a similar level on day 60 (day 60: 26.1 +/- 7.0 N/mm per gram; day 60 vs day 15: P = .937). More force was required to reach YP in C57 on day 3 (C57: 72.5 +/- 14.7 vs MRL: 19.9 +/- 1.6 N/g; P < .001) but not on either day 15 (C57: 156.1 +/- 27.5 vs MRL: 109.2 +/- 26.0 N/g; P = .120) or on day 60 (C57: 143.4 +/- 26.5 vs MRL: 164.5 +/- 18.7 N/g; P = .412). There was a significant decrease in BP in both strains on both day 15 and day 60 compared with day 3 postpartum (P = .856 for strain, P = .008 for day). MRL mice displayed significantly less cervical collagen birefringence compared with C57 control (P < .001) but increased proteoglycan staining and increased water content.


CONCLUSIONS
We provide evidence that genetic makeup may have an impact on cervical tissue remodeling and function. There are significant differences in postpartum cervical stiffness and compliance that vary with the regenerative collagen remodeling phenotype.
Buhimschi
Catalin S
CS
Department of Obstetrics, Gynecology, and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA.
Sora
Nicoleta
N
Zhao
Guomao
G
Buhimschi
Irina A
IA
D000818:Animals; D001696:Biomechanical Phenomena / Q000235:genetics*; D002584:Cervix Uteri / Q000502:physiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D049590:Postpartum Period / Q000235:genetics*; D013997:Time Factors