Evidence of compensatory elastin remodeling in non-prolapsed uterosacral ligaments and its divergence in histopathological subtypes of pelvic organ prolapse

Regenerative remodeling of the pelvic floor after labor and delivery restores pelvic organ positioning. In some individuals, accumulated tissue damage leads to failure of support structures, including the uterosacral ligament (USL) resulting in the descent of pelvic organs into the vaginal canal referred to as pelvic organ prolapse (POP). We hypothesized that consistent USL connective tissue changes occur as POP develops. USL biopsies from patients undergoing surgery for POP, or for benign gynecologic conditions without prolapse, were categorized anatomically (POP-Q) and histopathologically (POP-HQ) into inflammatory (POP-I), adipose (POP-A), or neointimal hyperplasia (POP-V) phenotypes. Histochemical and immunohistochemical methods identified and highlighted elastin and collagen fibers, and myofibroblasts. Control USLs possessed increased elastin as vaginal parity increased (p < 0.05) indicating an attempt at repair, but not with increasing age or BMI. POP-HQ subgroup USLs failed to show this increase. Progressively, Control and POP-V USLs whose uterus-vaginal complexes descended further into the vaginal canal, contained less elastin. Control and POP-A USLs possessed less elastin than POP-I and POP-V (p < 0.05) but trended towards having more collagen. POP-V USLs contained increased numbers of myofibroblasts and more arterial tunica intima elastin (p < 0.05). Increased numbers of myofibroblasts were also noted within POP-A smooth muscle fascicles. Collectively, these findings reveal an inherent reparative capacity in non-prolapsed uterosacral ligaments that appears dysregulated in different histopathological prolapse subtypes, suggesting divergent underlying pathways that we hypothesize may inform future personalized therapeutic strategies.