Pathophysiology of Pelvic Organ Prolapse

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Failure of pelvic organ support: potential mechanisms

The pelvic floor comprises several different tissue types that act in concert to provide support and maintain normal physiologic function of the rectum, vagina, urethra, and bladder. All tissue types of the pelvic floor are important for normal support of the pelvic organs, and failure of one or more of the tissue support systems may be involved in the pathophysiology of pelvic organ prolapse.

Interactions between levator ani and connective tissues of the pelvic floor

Ligaments and connective tissues surrounding the pelvic organs support and stabilize the organs in their position above the levator ani. Several connective tissue types are involved in this support system as discussed below.

Collagen

It has been suggested that abnormal synthesis or degradation of collagen and elastin fibers of the vaginal wall contributes to the pathophysiology of prolapse. The extracellular matrix of connective tissues comprises predominantly fibrillar collagens and elastic fibers embedded in a nonfibrillar ground substance of proteoglycans, glycosaminoglycans, and hyaluronan. Collagen synthesis in pelvic floor connective tissues in women with pelvic organ prolapse has been reviewed comprehensively.34

Lessons learned from mouse models of pelvic organ prolapse

As discussed in the introduction to this article, epidemiologic studies indicate that vaginal birth and aging are two major risk factors for developing pelvic organ prolapse. Nevertheless, the specific effects of pregnancy, parturition, and aging on pelvic floor support mechanisms have not been identified. Progress in this area has been hampered by the lack of readily available animal models to study the disease. Recent findings in mice with null mutations in genes that encode proteins involved

Elastic fiber: linking cells with their matrix

Cells within tissues specifically contact other cells. They also contact a complex network of secreted proteins and carbohydrates, the extracellular matrix. Animals contain many different types of extracellular matrices, each specialized for a different function. For example, tendons exhibit great strength, the extracellular matrix in the kidney is designed for filtration, and the uterus expands dramatically during pregnancy. Many tissues, including the uterus, cervix, and vagina, need to be

Elastic fibers and aging

Elastin is produced early in life. Production of elastin reaches peak levels in the third trimester of fetal life and steadily decreases during early postnatal development. In undisturbed tissues, elastic fibers may last over the entire human lifespan. In a transgenic mouse line bearing a reporter linked to the elastin promoter, activity of the elastin promoter increases during postnatal development, reaching a peak at 3 months of age in skin, then decreases.77 In many respects, age-related

Fibulin-5 and elastogenesis

Other proteins, including the emerging family of fibulin proteins, contact elastic fibers in vivo and are thought to promote the formation and stabilization of the fiber.67, 68 The term fibulin is derived from the Latin word for clasp or buckle. Fibulins comprise five family members, each with overlapping, but distinct, patterns of expression. They are particularly prominent in tissues rich in elastic fibers, such as lung, blood vessels, bladder neck, and uterus. Recent studies67, 68 identified

Elastic fibers in the vaginal wall of women with pelvic organ prolapse

In 1975, el-Kholi and Mina,81 using Verhoeffe's Van Geison stain, studied elastic fibers from the vaginas of 48 women of different age groups with and without vaginal prolapse. Elastic fibers were minimal and showed marked fragmentation in women with pelvic organ prolapse compared with those in age- and parity-matched controls. A more recent investigation failed to find significant abnormalities in vaginal wall elastic fiber staining. According to investigators, the photomicrographs in this

Summary

The pelvic floor is a complex dynamic system that supports the vagina and pelvic viscera. In women, failure of pelvic organ support is common. A wealth of literature has established that vaginal parity and aging are important risk factors for pelvic organ prolapse in women. The specific mechanisms by which vaginal delivery and aging lead to failure of pelvic organ support are unknown. For decades, pelvic surgeons have recognized that women with prolapse often exhibit abnormal connective tissues

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    Grant support: National Institutes of Health AG 028048.

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