Anatomy and Composition

The pelvic floor is a highly complex heterogeneous structure that orchestrates support to the vagina, which in turn provides support to the pelvic organs. In certain cases, such as childbirth, substantial stretch and accommodation of pelvic floor structures must also occur. Although the precise physiology by which the pelvic floor provides support to the vagina is not understood, it is known to comprise an amalgamation of skeletal muscles, connective tissue supports, and bones. Together, this support mechanism serves to maintain the location and orientation of the uterus, cervix, vagina, bladder, urethra, and the anorectum within the pelvis.

The pelvic floor musculature is largely composed of skeletal, or striated, muscle. The predominant muscle group is the levator ani muscles, which are the iliococcygeus, pubococcygeus, and puborectalis muscles. The pelvic floor forms the bottom of a bowl that extends anteriorly to the abdominal wall and posteriorly to the back and spine. Abnormal forces originating from the anterior or posterior trunk, from within the abdomen, or from the pelvic floor itself may affect its function. This includes the development of pelvic floor myalgia as can be seen after lower back injury, or the effect of chronic cough as an instigating factor for the development of pelvic organ prolapse.

In the human, the nervous system is divided into the central and the peripheral nervous systems (see Chapter 4 ). The central nervous system is typically considered to include the brain and spinal cord, whereas the peripheral nervous system encompasses the somatic and autonomic nervous systems. Somatic nerves primarily innervate skeletal muscle and allow a human to perform voluntary, self-directed actions. Conversely, the autonomic nervous system underlies baseline, homeostatic functions that occur without conscious thought or action. This includes innervation of the smooth muscle of visceral organs, the cardiac system, and glandular functions.

Somatic innervation to the levator ani muscles is supplied by efferent (motor) nerves specifically arising from the pelvic nerve (originating from spinal cord levels S2-S4) supplying the peritoneal aspect and the pudendal nerve (also from S2-S4) supplying the caudal, or perineal, portion. The levator ani muscles maintain a baseline contractile tone that helps to preserve the orientation of the pelvic organs ( ), which was originally termed the postural reflex of the pelvic floor ( ). This constant tone is dependent on proprioceptive afferent input as processed by the dorsal root ganglia in the spine and the normal function of afferent sensory nerves. Humans can voluntarily increase their pelvic muscle contractions, such as in response to an increase in intra-abdominal pressure, but the muscles rapidly fatigue and tone returns to baseline after an average of 1 min ( ). As humans evolved to become bipedal creatures and obtained upright postures, new stress forces emerged that began to be countered by the musculature. The pubococcygeus and puborectalis muscles bilaterally attach to the pubic bone just lateral to midline and wrap posteriorly around the rectum, forming a sling observed anatomically as the anorectal angle. The iliococcygeus originates from a connective tissue condensation (termed the arcus tendineus levator ani ) of the lateral pelvis near the ilia of the bony pelvis and attaches to the coccyx. This large muscle has a horizontal orientation and coalesces with the pubococcygeus and puborectalis to form the levator plate (median raphe), upon which the upper two thirds of the vagina and the uterus rest horizontally. The urethra, vagina, and rectum descend through the interior of this loop in the space termed the urogenital hiatus. As the levators contract, they apply pressure to these structures and eliminate potential space. Caudal to the levator plate, the vagina and rectum terminate in a vertical orientation.

Smooth muscle fibers are also present, primarily contained within viscera, including the bladder, urethra, uterus, vagina, and bowel. They allow for stretch and accommodation during filling of the viscera and evacuation of visceral contents in combination with autonomic reflexes. Smooth muscle cells can be found, to varying degree, within the supportive connective tissue. Many of the components of the pelvic floor are noted to be altered in postmenopausal women or women with prolapse, and the smooth muscle cells are no exception. For example, , using computer-based analysis, determined that the predicted proportion of smooth muscle cells in the round ligament is decreased in women with prolapse.

In orthopedic terminology, ligaments are the dense connective tissue connections bridging from bone to bone whereas tendon is the term given to the connection between a muscle and a bone. Within the abdomen and the pelvis, the term ligament is used more variably. A ligament may refer to a fold of peritoneum that formed during embryonic development. An example is the hepatoduodenal ligament, which contains the portal triad of the hepatic artery, portal vein, and the common bile duct. In the pelvis, the ligaments typically refer to the connective tissue suspensions tethering the viscera (such as the uterus, bladder, urethra, vagina, and rectum) to the pelvic sidewall and the bony pelvis. Condensations of connective tissues that provide support to the vagina and uterus include the cardinal-uterosacral ligament complex and the paravaginal attachments to the arcus tendineus fasciae pelvis (ATFP). This is collectively known as the endopelvic fascia.

The endopelvic fascia is a continuation of the web of connective tissue originating at the level of the uterine artery’s insertion at the uterus and extending bilaterally to the pelvic sidewalls and caudally to suspend the cervix and vagina. Close to the uterus and cervix it is termed the parametrium , and at the level of the external cervical os it becomes the paracolpium ( ). This web periodically solidifies into thicker bands called ligaments , which serve to support the internal organs of the pelvis and are primarily bridges between the viscera and bony structures. DeLancey and others have previously discussed a conceptual framework organizing these connective tissue attachments into levels corresponding to support of different anatomic sites on the vagina ( ) (see Fig. 2.10 ). Level I refers to the support of the vagina at its apex, specifically referring to the cardinal and uterosacral ligaments. Level II is the lateral support of the midportion of the vagina, where the endopelvic fascia coalesces with the ATFP on either side. More distally, there is also an attachment between the vagina and the arcus tendineus fascia rectovaginalis. Level III is the support of the distal vagina, specifically to the perineal body and the perineal membrane. Injury at different levels will cause different anatomic defects.

The connective tissue itself is composed of a mixture of collagen, elastin, proteoglycans, and the extracellular matrix (ECM) that acts as scaffolding for the other components. Collagen provides the tissue with tensile strength, and elastin provides resilience, which is the ability for tissue to snap back into place after it is deformed or stretched. Large and small proteoglycans are extracellular proteins important for cell-to-cell connections, or connections between cells and the ECM. Through the binding of small proteoglycans (decorin, fibromodulin, biglycan, luminican, and chondroadherin) with glycosaminoglycans, they form complexes that occupy space within the ECM and help it to resist compression ( ). Other proteoglycans, including fibronectin, vitronectin, and laminin, serve to create cell-to-cell bindings ( ). The composition of the connective tissue is dynamic, with production and degradation of collagens occurring as the tissue continuously remodels in response to stresses, aging, and injury. Tissue breakdown occurs after the enzymatic activity of acid cathepsins, which break down the protein cross-linked bonds that bind collagen fibers together, and matrix metalloproteinases (MMPs), which lead to cleavage of the collagen fibers themselves ( ).

Of the 19 known types of collagens, types I and III are found most commonly in epithelial tissues ( ). Overall, type I is the collagen found most commonly throughout the body. It forms large fibers and provides much of the tensile strength for tissues. Types II and III also form strong fibers that do not readily deform. Type III fibers are smaller than those formed by type I fibers. Type III collagen is typically found more frequently in tissues that require flexibility, such as the walls of blood vessels ( ). Type IV collagen assembles into a network configuration instead of distinct fibers, and it may help form the basement membrane beneath the fibers ( ). Type V collagen forms small fibrils and is frequently found in wound healing. It also likely directs fibrillogenesis. Heterogeneous fibrils are formed when type I collagen copolymerizes with type III or type V collagens. As the proportion of type III and IV collagens increase as compared with type I collagen, the tissue becomes weaker.

It is thought that hormones may influence the balance of collagen types within the tissues. After menopause, if hormone replacement therapy is not initiated, the amount of type I collagen decreases by 75% (compared with premenopausal women) and the ratio of type I-to-type III/V collagen is found to decrease in biopsies from the ATFP ( ). Thus, after menopause, there is an increased proportion of type III and type V collagens in human connective tissue. This group found no difference in the proportion of elastin or smooth muscle between pre- and postmenopausal women.

Changes in collagen composition are also likely associated with pelvic organ prolapse. found that the total collagen content of tissue and the solubility of that collagen were decreased in premenopausal women with prolapse as compared with control subjects. In their experiments, there was no change in the collagen I-to-collagen II ratios. They also found that MMP and cathepsin activity increased for prolapse patients, leading to more rapid turnover of the collagen ( ). Overall, the changes in collagen likely change the tensile strength of the tissue, a risk factor for prolapse. It is interesting to note that the collagen content is also decreased for women with prolapse in tissues that do not provide structural support, such as the cervix ( ).

Function and Biomechanical Properties

In nonhuman mammalian species, especially for animals that walk on four legs, the levator ani muscles primarily control the movement of an animal’s tail, and the connective tissue alone acts as the primary support structure ( ). For example, the rat has connective tissue anatomy that parallels human anatomy in terms of its support. The rat has attachments between the upper vagina and the spine, similar to the human uterosacral ligaments and the Level I support; paravaginal attachments between the lateral vagina and the dense connective tissue stretching from the pubic symphysis to the lateral bony pelvis, similar to the ATFP at Level II; and attachments emulating Level III support, connecting the distal vagina with the anterior surface of the ischiopubic rami ( ).

In humans, because of the adoption of an upright posture, the levator ani muscles and the connective tissue structures share the load. The muscles and the endopelvic fascia work together to support the pelvic organs. When the pelvic floor muscles contract at baseline, the tension applied to and experienced by the supportive ligaments is reduced. If the muscles are damaged, such as may happen after childbirth, or if the nerves that supply the muscles are stretched or otherwise damaged, such that the muscles they supply are compromised, then the shelf supporting the pelvic organs may sag or the uterus, cervix, bladder, and rectum may change their orientation or herniate through the urogenital hiatus. When the organs change their position, additional tension is placed on the supporting connective tissue, which may then stretch or even rupture, leading to observable pelvic organ prolapse. It is likely that vaginal childbirth serves as an initial instigating event for damage, but it is also likely that progressive denervation of the muscles continues to occur as a woman ages. Some suspect that pudendal nerve trauma (i.e., stretch and elongation during childbirth) may play a role, although this remains a point of contention. Other risks include chronic increased intra-abdominal pressure or repetitive high-pressure straining, such as occurs for patients with obesity, chronic cough conditions, chronic obstructive pulmonary disease, habitual heavy lifting, or chronic constipation.

Recent work has sought to elucidate the biomechanical properties of the pelvic floor. The pelvic floor by default is load-bearing, supporting the pelvic organs against the effects of gravity and applied intra-abdominal pressure. Hence, the standard components of biomechanics, including force application, stress deformation, and structural movement, will have an obvious effect on its function.

Applicable biomechanical parameters to this discussion include materials science terms including deformation , which is the general term given to the change in size or configuration of a material due to the actions of an external force or change in temperature. Deformation is also called strain . The force may be a tensile force, occurring because of pulling; a compression force, applied by pushing; or torsion, which is applied by twisting. The connective tissue within ligaments typically contributes to their viscoelastic property—the ability to initially resist strain, then to stretch as they begin to deform, and then to snap back and regain their previous configuration once the force is removed. If enough strain is experienced by the tissue, it may lose its recoil ability and undergo structural failure, in which rupture occurs. As an example from the orthopedic literature, we know that after ligaments are damaged, their collagen remodels as they heal. After healing from injury, the composition of the ligament changes; it is frequently stiffer and may be permanently stretched and elongated, losing its ability to recoil normally ( ).

Biomechanical properties may be structural or mechanical. This was well described by . Structural properties describe how tissues react when a load or force is applied; they are dependent on the actual size and shape of the tested tissue. Thus, a larger tissue sample generally performs better than a smaller tissue sample. An example is a uniaxial load-elongation test to failure ( Fig. 5.1 ; ). In this test, one edge of a tissue sample is rigidly fixed, and the other is connected to a movable arm, which stretches the tissue until the point of failure. The length that the tissue stretches as well as the force applied can be measured. The linear stiffness of the tissue is the slope of the load-elongation curve.

Structural properties are frequently measured using a uniaxial load-elongation test to failure, resulting in a load-elongation curve for the tissue complex.

(Modified with permission from Abramowitch SD, Feola A, Jallah Z, Moalli PA. Tissue mechanics, animal models, and pelvic organ prolapse: A review. Eur J Obstet Gynecol Reprod Biol . 2009;144(suppl 1):S146–S158.)

Measurement of mechanical properties is different because these properties take into account the differing sizes and shapes of a tissue sample. To obtain these formulas, the force applied to the tissue is divided by the specific cross-sectional area of the tissue; this is the stress. Measurement of mechanical properties also allows quantification of strain by calculating the difference in length from the original to the stretched tissue after the force is applied. As these properties are calculated per unit area, we believe they provide a more direct biomechanical measurement of the microcomposition of a tissue. For the particular tissue, how does its collagen, elastin, and smooth muscle composition contribute to its function? This is typically measured via a uniaxial tensile test to failure, also known as a stress-strain curve ( Fig. 5.2 ; ). Here, the tissue is clamped on at least two sides. Lengthening and stress sustained can be measured. The tangent modulus (also called the elastic modulus or Young’s modulus ) is the slope of this curve, and the tensile strength of the tissue is the maximal stress it can support. Of note, the tensile strength of a tissue may differ depending on the axis in which it is stretched—whether it is pulled linearly to the majority of muscular or connective tissue components or whether it is pulled perpendicularly. This differential stretch behavior is termed anisotropy .

Mechanical properties are frequently measured using the uniaxial tensile test to failure, resulting in a stress-strain curve.

(Modified with permission from Abramowitch SD, Feola A, Jallah Z, Moalli PA. Tissue mechanics, animal models, and pelvic organ prolapse: A review. Eur J Obstet Gynecol Reprod Biol. 2009;144(suppl 1):S146–S158.)

Stretch must occur during childbirth. As the fetal head descends into the pelvis from the uterus, through the cervix, and into the vagina, it must by definition pass through the urogenital hiatus. The bones of the fetal skull differentially deform based on whether the fetus is preterm or is at term, the shape of the mother’s pelvis, and the force of the expulsive labor efforts, but the head still must narrow and elongate as molding occurs during the second stage of labor. It is estimated that the average suboccipito-bregmatic diameter, the smallest aspect of the presenting fetal head, is 9.2 cm ( ) after molding. The urogenital hiatus is estimated to be 2.5 cm transversely from medial border to medial border between the levator ani muscles in an average nonpregnant woman without prolapse ( ). During delivery, the urogenital hiatus must rapidly dilate, similar to the dilation of the cervix but over a much shorter time frame. The particular biomechanical property affected is the stretch ratio, an extension of the normal strain described previously. The stretch ratio is a term referring to the ratio between the length of a tissue under stretch over the length of the tissue at rest. determined a maximum stretch ratio of 1.5 before muscle tissue undergoes structural failure, with subsequent rupture of muscle fibers. Using computer modeling of magnetic resonance images of the pelvis obtained from a nulliparous woman and simulating the passage of a fetal head through the pelvic floor model, found that the medial portion of the pubococcygeus muscles stretched the most, with a stretch ratio of 3.26, but that 79% of the simulated muscles had a stretch ratio greater than 1.5. Thus, it is likely that most vaginal deliveries lead to some amount of permanent stretch damage to the muscles of the pelvic floor.

Compared with other medical fields such as orthopedic surgery, female pelvic medicine and reconstructive surgery is in its infancy in terms of research into the biomechanical principles that apply to our work. We are only beginning to understand the effect of injury of the pelvic floor as a result of childbirth, the application of chronic pressure because of obesity or recurrent Valsalva with heavy lifting, chronic constipation or cough, or other trauma to the pelvic floor. Likewise, we have poor understanding of the healing and repair mechanisms undertaken by the pelvic soft tissues after injury. In the future, it will be critical to improve our understanding of all of these components if we are to have confidence in our understanding of the mechanisms of pelvic organ prolapse and to improve the longevity and specificity of our surgical corrections.

Anatomy and Composition

The vagina is composed of muscular and connective tissue elements. It is also richly vascular. The vagina is commonly described as a fibromuscular tube extending from the cervix to the perineum. The layers of the vagina include an epithelial surface, the lamina propria, the vaginal muscularis, and the adventitia. The surface of the vagina is lined with stratified squamous epithelial cells that are nonkeratinizing. Histologically, there are four main epithelial layers: (1) most superficially, nonkeratinized cells with small, pyknotic nuclei; (2) an intermediate glycogen-containing cellular layer; (3) proliferating parabasal cells; and (4) the basal epithelial layer ( ). Adjacent to the epithelium is the lamina propria, or subepithelium, a layer of dense connective tissue that is composed of collagen and elastin. Next is the muscularis, which is largely composed of smooth muscle cells. The smooth muscle adopts a circular configuration for its inner layer and then a longitudinal orientation in its outer layer ( ). Intercalated between the smooth muscle bundles of the muscularis are blood vessels. Finally, the adventitia is a layer of loose connective tissue and contains collagen, elastin, additional smooth muscle, and additional vasculature. The composition of the connective tissue here includes 84% collagen and 13% elastin ( ). Overall, the vagina and the endopelvic fascia are very similar in terms of their collagen configurations ( ). Thus, clinically obtained vaginal biopsies may allow extrapolation to the collagen composition of the endopelvic fascia for a particular patient.

Embryology and Innervation (Also See Chapter 3 )

The innervation differs between the proximal and distal portions of the vagina, and these differences begin early in embryogenesis. Embryologically, the distal two thirds of the vagina arises from an outgrowth of the endoderm of the urogenital sinus, the paired sinovaginal bulbs. The proximal one third of the vagina, as well as the cervix and the uterus, arise from the uterovaginal primordium, which is the result of fusion of the paramesonephric ducts in the midline. The solid sinovaginal bulbs eventually fuse together, grow cephalad, and then fuse with the uterovaginal primordium. This whole structure then eventually canalizes to form the vagina. The original junction between the sinovaginal bulbs and the urogenital sinus is the site of the future hymen. Reflecting differential embryologic origins, innervation to the upper portion of the vagina is via the inferior hypogastric nerve plexus, and innervation to the lower vagina and skin is from the pudendal nerve. The spinal origin of all of these nerves is the sacral levels S2 to S4 ( ).

Important to note is the convergence of sensory input from the pelvis at the level of the spinal cord and the brain. Although afferent sensations are tracked independently from various end organs (bladder, ureters, vagina, the skin), there is dynamic processing of the inputs centrally, such that pathophysiology from one organ may affect others. This helps to explain the expression of numerous pelvic pain syndromes within the same individual, such as endometriosis, interstitial cystitis, irritable bowel syndrome, and fibromyalgia. There may also be overlap of the sensory nerve fibers within the pelvic nerve plexus.

Orientation and Structural Support

The vagina contains a convex angle, with the uppermost portion in a nearly horizontal orientation as it rests on top of the levator muscles and the distal portion descending more vertically. The angle occurs as the vagina descends through the genital hiatus and is caused by the sling of levator muscles contracting at baseline. found this angle to average 130° in the supine position on X-ray vaginogram. The levator plate helps to withstand downward forces caused by Valsalva maneuvers or other increases in intra-abdominal pressure. For example, if this angle is lost because of a lack of tone of the puborectalis muscle or a compromise in the connective tissue attachments, the genital hiatus will widen and the risk of prolapse and herniation through the genital hiatus increases ( ). This clinically has practical effects when considering the approach for a prolapse repair. Any repair that changes the angle of the vagina may circumvent this normal anatomic support. For example, using magnetic resonance imaging of supine women, the average angle was found to be 145°. Two different investigative groups confirmed differential postoperative angles after different surgical procedures; after abdominal sacrocolpopexy with Burch colposuspension, the angle was 137° to 149°, and after sacrospinous ligament fixation the angle was increased at 215° to 220° ( ). In considering these examples, it is important to remember that the normal anatomy has already been disrupted, leading to the prolapse. However, on the basis of imaging studies, it appears that sacrocolpopexy leads to a better restoration of the normal angle than does sacrospinous ligament fixation.

Because of its attachments to the ATFP and the arcus tendineus rectovaginalis, the midvagina in cross-section for a woman with normal support has an “H” configuration. This has been confirmed on magnetic resonance imaging ( ).

Overall, the vaginal epithelium contributes little structural strength on its own. Instead, structural integrity is supplied by the deeper layers of connective tissue and smooth muscle ( ).

Function

The normal functions of the vagina include response to hormonal stimulation, lubrication and stretch during sexual activity, immunologic protection to help protect against the acquisition of infectious diseases, and remodeling and stretch to allow for vaginal childbirth.

As a premenopausal woman traverses the menstrual cycle, the vaginal epithelium responds to fluctuating hormone levels. collected vaginal biopsies from women every third day throughout the menstrual cycle. They reported that the epithelium normally thickens and superficial epithelial cells mature when circulating estrogen levels are high. Under high progesterone levels, superficial cell layers are shed and the basal portion of the epithelium is more quiescent. Proliferation is confined to the parabasal cell layer. At the time of ovulation, the epithelium is maximally thickened and mature.

One of the consequences of sexual excitation is genital congestion, which is thought to be a reflexive autonomic response. The major neurotransmitters involved with this response are nitric oxide, which acts on the clitoris, and vasoactive intestinal polypeptide (VIP), which affects the vagina. There may be other neurotransmitters that have not yet been identified. With this reflexive response, the genitals become engorged and lubrication is increased. This is partly mediated by increased vascular flow and is dependent on estrogen. After menopause, paravaginal vasodilation is compromised because of a decrease in the number of estrogen receptors on the vascular endothelium, and it may lead to deficits in the genital congestion response ( ).

Before menarche, the vaginal epithelium is thin and the vaginal pH is relatively high (pH > 4.7). As endogenous estrogen production is initiated by the ovaries, the vaginal epithelium thickens and glycogen levels in the epithelium increase. Once a woman begins menstruating, the vagina maintains a pH in the acidic range (pH < 4.5). It is thought that this pH level is established as the naturally predominant Lactobacillus bacteria ferment the glycogen present in the vaginal epithelium, converting it into lactic acid ( ) Lactobacilli also produce hydrogen peroxide, contributing to the acidic environment. After menopause, as serum estrogen levels decrease, estrogen receptors are subsequently downregulated in the epithelium. The proportion of intermediate and parabasal cells in the epithelium increases, with few superficial basal cells seen. There is less vaginal blood flow. The vaginal epithelium thins and elasticity is reduced. Normal vaginal secretions decrease, and glycogen stores decrease. This results in a higher baseline vaginal pH level ( ). Estrogen receptors are restored and vaginal pH returns to an acidic level if exogenous estrogen hormone therapy is administered ( ). There is currently a large body of research examining biofilms and other immunologic defenses of the vagina in preventing infection.

One of the critical functions of the vagina is to stretch to allow for the vaginal delivery of offspring. However, vaginal parturition has long been recognized as a major risk factor in the development of pelvic organ prolapse, and new research has attempted to elucidate the mechanism of the development of this disease. Throughout the body, elastin is generally a stable and permanent component of tissue. It is remarkable that, in the vagina, elastin is actually resynthesized after childbirth. Rodent models of pelvic organ prolapse have been developed in which proteins important for elastin fiber assembly have been genetically knocked out, including null mutations in lysyl oxidase-like-1, as reported by and , and fibulin-5, as reported by . Both of these rodent models demonstrate pelvic organ prolapse associated with pregnancy.

Biomechanical Properties and Histology

The biomechanical properties of the vagina likely demonstrate anisotropy, as previously defined. Hence, vaginal tissue behaves differently when it is stretched longitudinally as compared with when it is stretched circumferentially. This is seen with the disproportional circumferential stretch necessary for vaginal parturition as compared with more moderate lengthening of the vagina.

performed an experiment examining longitudinal anterior vaginal wall tissue samples from pre- and postmenopausal women, all with prolapse. This study did not control for hormone replacement therapy use. Samples were normalized by cross-sectional area. No differences in elongation length or deformation amount were found, but an increased elastic modulus was found, which indicated increased stiffness in postmenopausal tissues. On the basis of the experiment, this may reflect age-related changes, but conclusions cannot be drawn regarding changes on the basis of prolapse status.

Subsequently, used similar techniques to test the biomechanical properties of pre- and postmenopausal Chinese women with and without prolapse. All vaginal samples were obtained in a longitudinal orientation from the midline anterior vagina at the time of hysterectomy. Subjects were controlled for hormone use and smoking history; no subjects were using hormone therapy, and all were nonsmokers. The mechanical properties of the tissue were measured, and stress-strain curves were calculated. For all patients with prolapse, the biomechanical properties of the tissues were inferior; they had shorter lengths of maximum elongation and fracture, and they had an increased elastic modulus. Overall, they concluded that for women with prolapse, the connective tissues had decreased elasticity and increased stiffness.

Thus, independent of postmenopausal status, prolapse itself is associated with histologic changes in the composition of the vagina. found a decreased proportion of smooth muscle cells in biopsies from the anterior vaginal wall of women with prolapse versus controls. Hence, these women have a greater fraction of collagen and ECM within the vaginal muscularis. In addition, the normally tightly organized smooth muscle bundles were less dense and less rigidly structured.

further present a hypothesis in regards to the decreased smooth muscle cells. One of the explanations could be apoptosis of these cells. After the programed cellular death of apoptosis, fibroblasts frequently enter the tissue and may produce de novo collagens, changing the collagen ratios. As discussed above, this has been observed in human tissue biopsies from various components of the pelvic floor and vagina. This may have direct clinical ramifications, especially in the consideration of vaginal graft materials such as synthetic mesh grafts. If the graft materials also lead to apoptosis, or hasten it in tissue already compromised and prolapsed, then could this hasten abnormal collagen production? These questions will be critical as next-generation graft materials are developed.