Myometrial Wound Healing Post-Cesarean Delivery in the MRL/MpJ Mouse Model of Uterine Scarring

Abstract

There is little known about healing of the uterus after Cesarean delivery (CD). Uterine wound repair was studied by using two strains of mice with different wound healing characteristics: MRL/MpJ؉/؉ (MRL: "high-healer" phenotype) and C57Bl/6 ("low-healer" phenotype). First, we examined the morphology and histology of the uterine wall repair. We identified wound granulation tissue 3 days post-CD in both strains, albeit less in the MRL strain. Macroscopically, no scar could be identified either in MRL or C57Bl/6 mice on day 60 post-CD. However, histologically, we found significant differences in wound integration, inflammation, and collagen birefringence between the two strains of mice. Using a histological index, we provided evidence for significant differences in mitotic activity in the initial phases of uterine healing among strains. Functional behavior of the uterine scar also was analyzed by using biomechanical parameters such as slope (measure of stiffness), yield point (measure of elasticity), and break point (measure of strength). There were significant differences in stiffness of the scarred myometrium between the two phenotypes. MRL mice displayed a significantly lower yield point compared with C57Bl/6. The break point was reached faster on days 15 and 60 in both C57Bl/6 and MRL strains compared with day 3 post-CD. Our findings indicate that differences in regenerative ability translate in histological , mitotic , and functional differences in biomechanical properties of the scarred myometrium after CD.

Why Do Niches Develop in Caesarean Uterine Scars? Hypotheses on the Aetiology of Niche Development

“…This suggests an individual predisposition for impaired wound healing caused by factors still unknown. In an animal model it has been demonstrated that genetic predisposition may affect histological and biomechanical wound healing of artificial myometrial defects (Buhimschi et al, 2010). Some studies in humans report an association between niche development and BMI, preeclampsia or hypertension (Osser et al, 2009).…”

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

“…Since that time, there have been many reports showing that multiple tissue types in MRL mice display healing responses. These include heart myocardium (Leferovich et al, 2001;Haris Naseem et al, 2007;Alfaro et al, 2008), digits (Chadwick et al, 2007;Gourevitch et al, 2009), articular cartilage (Fitzgerald et al, 2008;Rai et al, 2012), intra-articular fractures (Ward et al, 2008), corneal epithelium (Ueno et al, 2005), CNS stem cells and tissue (Hampton et al, 2004;Baker et al, 2006;Balu et al, 2009;Thuret et al, 2009), central and peripheral nerves (Buckley et al, 2011;Thuret et al, 2012) and myometrial healing (Buhimschi et al, 2010). Further, dorsal skin wounds repaired with skin transplants also show enhanced healing without scarring in MRL (Tolba et al, 2010).…”

Rupture of the posterior cul-de-sac during trial of labour after caesarean section

“…Fibrosis of the old caesarean scar could have caused a stronger mechanical force on the posterior cul-de-sac which might explain the rupture 10. It could possibly explain why half of the cases with posterior fornix rupture in the literature were in women with a previous caesarean section.…”