Loss of Elastic Fibers Leads to Incontinence, Other Pelvic Floor Disorders

Newswise — It is estimated that up to half of U.S. women suffer from some level of female pelvic floor disorders (FPFD), a group of conditions that includes pelvic organ prolapse, urinary incontinence, and other sensory and emptying abnormalities of the lower urinary tract. Risk factors include vaginal childbirth and aging, yet little is known about the underlying molecular mechanism that causes the weakening of the pelvic support structures.

Scientists at the Berman-Gund Laboratory at the Massachusetts Eye and Ear Infirmary (MEEI) and Harvard Medical School (HMS) are a step closer to understanding the cause of FPFD. In a study published in the February issue of the American Journal of Pathology, the researchers found a failure to replenish elastic fibers in mice causes pelvic floor disorders like those found in humans.

Elastic fibers confer resilience to the skin and many other connective tissues. Not surprisingly, the female reproductive organs and pelvic floor are rich in elastic fibers. These tissues undergo massive change during pregnancy and childbirth. The problem occurs when elastic fibers are not properly replenished and the tissues fail to return to their natural shape. According to Tiansen Li, Ph.D., HMS associate professor of ophthalmology, a principal investigator at the Berman-Gund Laboratory at MEEI, and senior author of the paper, mice with a defective lysyl oxides-like-1 protein (LOXL1), which they have already shown to be critical for elastic fiber maintenance, replicate major clinical manifestations of human FPFD. LOXL1 is essential for remodeling elastic fibers and keeping tissues in their place. His team used a mouse model in which they "knocked out" the LOXL1 gene.

"In this study, we showed that mutant mice lacking LOXL1 develop complex and severe pelvic floor disorders," Li said. "The important question now is whether loss of elastic fibers, either because of age and/or genetic predisposition, underlies the etiology of common pelvic floor disorders among older women."

Future directions that arise from the current study are to demonstrate, by way of clinical studies, that an elastic fiber defect underlies the pathophysiology of human FPFD and to develop therapeutic strategies aimed at enhancing the elastic fiber system in the pelvic tissues. Conceivably, supplementing LOXL1 by protein or gene therapy could potentially be developed into a valid therapeutic approach for women at high risk for FPFD.

This work was supported by a grant from the Ruth and Milton Steinbach Fund.

MASSACHUSETTS EYE AND EAR INFIRMARYhttp://www.meei.harvard.eduThe Massachusetts Eye and Ear Infirmary, an independent specialty hospital, is an international center for treatment and research and a teaching hospital of Harvard Medical School. HARVARD MEDICAL SCHOOLhttp://hms.harvard.edu/ Harvard Medical School has more than 7,000 full-time faculty working in 10 academic departments housed on the School's Boston quadrangle or in one of 48 academic departments at 18 Harvard teaching hospitals and research institutes. Those Harvard hospitals and research institutions include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, The CBR Institute for Biomedical Research, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Massachusetts Mental Health Center, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and the VA Boston Healthcare System.