Pregnancy and age differentially affect stiffness, injury susceptibility, and composition of murine uterosacral ligaments

Pelvic organ prolapse is a debilitating condition that diminishes quality of life, and it has been linked to pregnancy and aging. Injury of the uterosacral ligaments (USLs), which provide apical support to the pelvic organs, is a major cause of uterine prolapse. In this study, we examined the effect of pregnancy and age on the apparent elastic modulus, susceptibility to collagen damage, and extracellular matrix (ECM) composition of the murine USL. USLs from mice at three different stages of pregnancy and across two age groups were mechanically tested and evaluated for collagen microdamage. Raman spectroscopy was used to evaluate changes in ECM composition. Our findings reveal that (1) all USLs subjected to mechanical stretch sustained collagen microdamage, (2) both pregnancy and age significantly affected USL stiffness and injury susceptibility, and (3) pregnancy, but not age, altered ECM composition. Overall, this work represents a major step toward understanding the role of tissue microstructure and mechanical function in USL injury, which should guide novel ECM-targeted treatment and prevention strategies for uterine prolapse.