FIGURE 4.

The disruption of normal elastic fiber homeostasis has been implicated in clinical manifestation of pelvic organ prolapse (POP). In this controlled study, we sought to ascertain the individual contributions of vaginal birth (parity), prolapse, and LOXL1 absence on maintenance of elastic fiber homeostasis, in a LOXL1 KO mouse model. Group‐wise comparisons relevant to each of these three effects are indicated by the respective colored arrows. We investigated changes in elastic matrix synthesis, cell proliferation, gene (RT‐PCR) and protein (western blots) expression for key elastic fiber assembly proteins, enzymes regulating matrix proteolysis and key signaling proteins (TGF‐B1 and BMP‐1) known to be implicated in elastin homeostasis. Primary outcomes pertinent to the three effects are indicated in the callouts. Our results suggest that the combination of inhibited elastin precursor synthesis, impaired cross‐linking, and poor elastin clearing creates an environment in which the vaginal ECM cannot properly repair itself after each delivery. Successive trauma sustained to the pelvic floor without proper repair could lead to POP