Twenty-nine patients aged 49 years with Stage II or more pelvic organ prolapse (POP) (according to the POProlapse Quantification (POPQ) staging criteria) were examined to study the role of the matrix proteins Fbln-5 and LOXL-1 in the connective tissue structures (fibroblasts, vascular endothelium, epithelium, and extracellular matrix) in the pathogenesis of POP. A control group consisted of 29 women with the normal pelvic floor. Morphological and immunohistochemical examinations were performed. The patients with POP were found to have impaired elastogenesis characterized by the altered elastic skeleton of the vaginal wall with decreased levels of the matrix proteins of Fbln-5 and LOXL-1 in the epithelium, vascular endothelium, fibroblasts, and extracellular matrix as compared to the same indicators in the healthy women. There was reduced Fbln-5 expression in the extracellular matrix of patients who had given birth twice or more and in those who had sustained maternal soft tissue injury in childbirth. These patients are at high risk for elastinopathy and subsequent POP.