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118: Genetic background impacts on myometrial wound healing post-cesarean delivery (CD): A MRL/MPJ+/+ mouse model of uterine scarring

      Objective

      Little is known about myometrial healing following CD. We investigated myometrial wound repair using 2 strains of mice [MRL/MpJ+/+ (MRL: “high-healer” phenotype) and C57BL/6 (C57: “low-healer” phenotype)] that differ significantly in their genotype and wound healing characteristics.

      Study Design

      MRL (n=18) and C57 (n=19) pregnant mice received BrdU in drinking water from day (d) 16 (term d19) of pregnancy. CD was performed on d17 by standardized technique. Ear punches were performed to confirm differences in healing phenotype. Mice were sacrificed at 3, 5, 15 & 60d post-CD (4-5 mice/d/strain). H&E and Sirus red were used for histological examination of the scar (wound integration, inflammation and collagen birefringence). Dividing cells were labeled using anti-BrdU antibody and a mitotic index was calculated. Stress-strain curves for scarred tissue were generated and analyzed for biomechanical parameters such as stiffness, elasticity and tissue strength.

      Results

      1) 60d post-surgery the ears of MRL mice healed completely without scarring (regeneration) while C57 mice maintained an open ear-hole; 2) Uterine wound granulation tissue was identified 3d post-CD in both strains but less in the MRL strain; 3) No scar could be macroscopically identified in either MRL or C57 mice 60d post-CD; 4) Significant histological differences in wound integration, inflammation and collagen birefringence were observed between the phenotypes; 5) Uterine mitotic activity commenced and ended earlier in MRL compared to C57 mice; 6) C57 uteri had increased stiffness and less elasticity compared to MRL at d15 & d60 post-CD.

      Conclusion

      This study provides a better understanding of myometrial wound healing after CD. The differences in regenerative ability of MRL and C57 mice suggest that uterine healing and functional behavior of the uterine scar is genotype dependent.