Functional Anatomy: Gynecology
In vitro functional responses of isolated human vaginal tissue to selective phosphodiesterase inhibitors.
Uckert S, Ehlers V, Nuser V, Oelke M, Kauffels W, Scheller F, Jonas U
World J Urol 2005 Nov 5;:1-7.
Only little is known as to the significance of the cyclic nucleotide-mediated signal transduction in the control of the function of human vaginal smooth musculature. Recently, the presence of the phosphodiesterase (PDE) isoenzymes 4 (cAMP-PDE) and 5 (cGMP-PDE) in the human vagina was reported. Thus, it was the aim of the study to elucidate the effects of some PDE inhibitors on the tension induced by endothelin 1 (ET-1), as well as on levels of cGMP and cAMP in isolated human vaginal wall tissue. Using the organ bath technique, the ability of norepinephrine (NE), carbachol, serotonin (5-HT), oxytocin and ET-1 to contract isolated vaginal wall muscle strips was evaluated. In another set-up, the effects of the PDE4 inhibitor rolipram and PDE5 inhibitors sildenafil and vardenafil (1 nM-10 muM) on the tension induced by 0.1 muM ET-1 of human vaginal wall tissue strips were investigated. In order to measure drug effects on tissue levels of cGMP and cAMP, vaginal tissue was exposed to different concentrations (0.1, 1 and 10 muM) of the compounds and the accumulation of cyclic nucleotides was determined. The adenylyl cyclase stimulating agents forskolin and nitric oxide donor sodium nitroprusside (SNP) (0.01, 0.1 and 1 muM) were used as reference compounds. While NE, carbachol and oxytocin failed to contract the vaginal tissue, ET-1 and, to a certain degree, 5-HT elicited contractile responses of the isolated strip preparations. The tension induced by 0.1 muM ET-1 was dose-dependently reversed by the drugs. The rank order of efficacy was sildenafil > forskolin > rolipram >/= vardenafil > SNP. R (max) values ranged from 24% (SNP) to 50% (sildenafil). With sildenafil being the only exception, none of the compounds reached an EC(50 )value. The relaxing effects of the drugs were paralleled by a fourfold to tenfold increase in tissue levels of cGMP and/or cAMP. Our results demonstrate that PDE inhibitors can relax human vaginal tissue and increase levels of cyclic nucleoside monophosphates. The findings with regard to the PDE5 inhibitors may indicate that the NO-cGMP pathway is, to a certain degree, involved in the control of vaginal smooth muscle tone. This might be of significance with regard to the pharmacological treatment of disorders connected with female sexual arousal and the ability to achieve orgasm.
Estrogen Replacement, Muscle Composition, and Physical Function: The Health ABC Study.
Taaffe DR, Newman AB, Haggerty CL, Colbert LH, DE Rekeneire N, Visser M, Goodpaster BH, Nevitt MC, Tylavsky FA, Harris TB
Med Sci Sports Exerc 2005 Oct;37(10):1741-1747.
PURPOSE: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to determine whether estrogen use is associated with enhanced muscle composition and, if so, whether this translates into improved strength and physical function. METHODS: Cross-sectional analysis of 840 well-functioning community-dwelling white women (current estrogen replacement therapy (ERT) users = 259, nonusers = 581) aged 70-79 yr participating in the Health, Aging and Body Composition Study. Muscle composition of the midthigh by computed tomography included cross-sectional area (CSA) of the quadriceps, hamstrings, intermuscular fat and subcutaneous fat, and muscle attenuation in Hounsfield units (HU) as a measure of muscle density. Isometric hand grip and isokinetic knee extensor strength were assessed by dynamometry. Physical function was assessed using a summary scale that included usual 6-m walk and narrow walk speed, repeated chair stands, and standing balance. RESULTS: In analyses of covariance adjusted for relevant confounders, quadriceps muscle CSA and HU were greater in current ERT than non-ERT women (P < 0.05). Grip strength was also greater (P < 0.05) in women taking ERT while knee extensor strength approached significance (P < 0.10). However, differences in muscle composition and strength were modest at </=3.3%. There was no difference by ERT status for the hamstring muscles, fat CSA, or for physical function. CONCLUSION: The associations between ERT and muscle composition and strength were minor and did not translate into improved physical function. Initiation of ERT for preservation of muscle composition and function may not be indicated.
The female athlete and menstrual function.
Goodman LR, Warren MP
Curr Opin Obstet Gynecol 2005 Oct;17(5):466-70.
PURPOSE OF REVIEW: In the past year, there have been remarkable advancements in the understanding of the female athlete's pathology and in recognizing the specific needs of women participating in both recreational and competitive sports. The purpose of this review is to highlight the recent developments in the field of female athletes and menstrual function. RECENT FINDINGS: Although the female athletic triad, consisting of disordered eating, amenorrhea and osteoporosis, has been clinically recognized, there have been few studies quantifying the long-term effects. This review summarizes recently explored topics, including: disordered eating as a main culprit of menstrual irregularities, long-term longitudinal studies following female athletes through to retirement, and current treatment options. SUMMARY: Understanding the causes, profiles and the prevention of menstrual irregularities in the female athlete should help decrease its prevalence among women involved in athletics. The literature reviewed in this article stresses the importance of early detection, as well as the consequences of eating disorders, menstrual disturbances and bone loss left untreated.
Impact of menopause on collagen subtypes in the arcus tendineous fasciae pelvis.
Wein AJ
J Urol 2005 Oct;174(4 Pt 1):1350.
Anatomy of the clitoris
O'connell HE, Sanjeevan KV, Hutson JM
J Urol 2005 Oct;174(4, Part 1 of 2):1189-1195.
PURPOSE: We present a comprehensive account of clitoral anatomy, including its component structures, neurovascular supply, relationship to adjacent structures (the urethra, vagina and vestibular glands, and connective tissue supports), histology and immunohistochemistry. We related recent anatomical findings to the historical literature to determine when data on accurate anatomy became available. MATERIALS AND METHODS: An extensive review of the current and historical literature was done. The studies reviewed included dissection and microdissection, magnetic resonance imaging (MRI), 3-dimensional sectional anatomy reconstruction, histology and immunohistochemical studies. RESULTS: The clitoris is a multiplanar structure with a broad attachment to the pubic arch and via extensive supporting tissue to the mons pubis and labia. Centrally it is attached to the urethra and vagina. Its components include the erectile bodies (paired bulbs and paired corpora, which are continuous with the crura) and the glans clitoris. The glans is a midline, densely neural, nonerectile structure that is the only external manifestation of the clitoris. All other components are composed of erectile tissue with the composition of the bulbar erectile tissue differing from that of the corpora. The clitoral and perineal neurovascular bundles are large, paired terminations of the pudendal neurovascular bundles. The clitoral neurovascular bundles ascend along the ischiopubic rami to meet each other and pass along the superior surface of the clitoral body supplying the clitoris. The neural trunks pass largely intact into the glans. These nerves are at least 2 mm in diameter even in infancy. The cavernous or autonomic neural anatomy is microscopic and difficult to define consistently. MRI complements dissection studies and clarifies the anatomy. Clitoral pharmacology and histology appears to parallel those of penile tissue, although the clinical impact is vastly different. CONCLUSIONS: Typical textbook descriptions of the clitoris lack detail and include inaccuracies. It is impossible to convey clitoral anatomy in a single diagram showing only 1 plane, as is typically provided in textbooks, which reveal it as a flat structure. MRI provides a multiplanar representation of clitoral anatomy in the live state, which is a major advantage, and complements dissection materials. The work of Kobelt in the early 19th century provides a most comprehensive and accurate description of clitoral anatomy, and modern study provides objective images and few novel findings. The bulbs appear to be part of the clitoris. They are spongy in character and in continuity with the other parts of the clitoris. The distal urethra and vagina are intimately related structures, although they are not erectile in character. They form a tissue cluster with the clitoris. This cluster appears to be the locus of female sexual function and orgasm.
Anatomical basis for nerve-sparing radical hysterectomy: immunohistochemical study of the pelvic autonomic nerves.
Maas CP, Kenter GG, Trimbos JB, Deruiter MC
Acta Obstet Gynecol Scand 2005 Sep;84(9):868-74.
BACKGROUND: Autonomic nerve damage plays a crucial role in the etiology of bladder dysfunction, sexual dysfunction, and colorectal motility disorders that occur after radical hysterectomy. We investigated the extent and nature of nerve damage in conventional and nerve-sparing radical hysterectomy. METHODS: Macroscopical disruption of nerves was assessed through anatomical dissection after conventional and nerve-sparing surgery on five fixed and one fresh cadaver. Immunohistochemical analysis of surgical margins was performed to confirm nerve damage using a general nerve marker (S100) and a sympathetic nerve marker (anti-tyrosine hydroxylase) within sections of biopsies. RESULTS: Macroscopical dissection showed that in the conventional procedure, transsection of the uterosacral ligaments resulted in disruption of the major part of the hypogastric nerve. After nerve-sparing surgery, only the medial branches of the hypogastric nerve appeared disrupted. Division of the cardinal ligaments in the conventional procedure identified the inferior hypogastric plexus running into the most posterior border of the surgical margin. The anterior part of the plexus was disrupted. Dissection of the nerves after the nerve-sparing procedure showed that this anterior part of the plexus was not involved in the surgical dissection line. Dissection of the vesicouterine ligament disrupted only small nerves on the medial border of the inferior hypogastric plexus in both techniques. Microscopical evaluation of the surgical margins confirmed the macroscopical findings. CONCLUSION: Conventional radical hysterectomy results in disruption of a substantial part of the pelvic autonomic nerves. The nerve-sparing modification leads to macroscopic reduction in nerve disruption which is substantiated by microscopical evaluation of surgical margins.
Menopause, physical activity, and body composition/fat distribution in midlife women.
Sternfeld B, Bhat AK, Wang H, Sharp T, Quesenberry CP Jr
Med Sci Sports Exerc 2005 Jul;37(7):1195-202.
PURPOSE: Hormonal changes associated with menopause, chronological aging, and lifestyle, specifically physical activity, may all influence the changes in body composition and fat distribution experienced by midlife women. This cross-sectional study examined those relations in a representative sample of 248 white and Chinese women, ages 47-57, participating in an ancillary study to the Study of Women's Health Across the Nation (SWAN), a multi-center, longitudinal investigation of the natural history of the menopause in a racially/ethnically diverse cohort. METHODS: Body composition (lean mass, percent body fat) was assessed with dual energy x-ray absorptiometry, and central adiposity was determined by waist circumference. Physical activity was assessed from 7 d of accelerometer recordings. Menopausal status was based on self-reported bleeding patterns. RESULTS: Higher levels of physical activity, particularly vigorous-intensity activity, were generally independently associated with decreased percent body fat and smaller waist circumference, although these findings were not statistically significant in the Chinese women. Among the white women, every half a standard deviation increase in total activity was associated with a 1.6-point decrease in percent body fat (P = 0.002). Waist circumference decreased from 96.2 cm (SE = 1.04) in those doing no vigorous-intensity activity to 81.4 cm (SE = 1.05) in those doing 10 min or more a day (P for trend = 0.05). For both the whites and the Chinese, late peri- and postmenopausal status was associated with lower lean mass, and among the Chinese, tended to be associated with higher percent body fat. CONCLUSION: These findings suggest that regular physical activity may help to mitigate the tendency for weight gain and adverse changes in body composition and fat distribution that accompany aging and the menopausal transition.
Short-term functional and neuroregenerative response of the urethra to ovariectomy and vaginal distension in female rats.
Ferguson CL, Lin DL, Rao S, Damaser MS
Int Urogynecol J Pelvic Floor Dysfunct 2005 Mar-Apr;16(2):119-25. Epub 2004 Oct 22.
The objective of this study was to investigate the effects of ovariectomy (OVX) and vaginal distension (VD) on leak point pressure (LPP) and pudendal nerve regenerative response in the female rat. Twenty rats underwent OVX 3 days prior to either VD or sham distension. Seventeen rats did not receive OVX but underwent either VD or sham distension. Four days after distension, LPP testing was performed. In situ hybridization for beta(II) tubulin mRNA, an indicator of the neuroregenerative response, was performed on motoneurons of the pudendal nerve. In the non-OVX group, LPP was significantly decreased after VD. After OVX, the difference in LPP between VD and sham rats did not quite reach the level of statistical significance. There was a statistically significant interaction between the effects of OVX and VD on LPP. There was no significant difference in in situ hybridization results between any of the groups. No neuroregenerative response of motoneurons of the pudendal nerve was observed after either VD or OVX.
Histologic evaluation of human cadaveric fascia lata in a rabbit vagina model.
Walter AJ, Morse AN, Leslie KO, Hentz JG, Cornella JL
Int Urogynecol J Pelvic Floor Dysfunct 2005 Jun 23;.
The purpose of this study was to evaluate the histologic response of human cadaveric fascia lata after vaginal implantation. Freeze-dried, gamma-irradiated cadaveric fascia lata from three lots was implanted between the rectovaginal membrane and vaginal epithelium in New Zealand white rabbits. Rabbits were killed at 2, 4, 8, and 12 weeks after implantation. At necropsy, gross findings were described and specimens for routine cultures were taken. Histologic evaluation determined graft integrity, neovascularization, inflammatory response, and host tissue incorporation. Nine rabbits were available for histologic analysis and 14 for gross and microbiologic analysis. Vaginal erosions occurred with three grafts. The remainder were adherent to the surrounding tissues. Erosion was associated with bacterial colonization of the graft. Autolysis of one graft occurred at 4 weeks. Over time, the inflammatory response decreased and neovascularization increased; by 12 weeks, the graft collagen was replaced by host collagen. Cadaveric fascia lata serves as scaffolding for host tissue incorporation with replacement by host collagen.
Estrogen increases collagen I and III mRNA expression in the pelvic support tissues of the rhesus macaque.
Clark AL, Slayden OD, Hettrich K, Brenner RM.
Am J Obstet Gynecol 2005 May;192(5):1523-9.
OBJECTIVE: Our aim was to study the effect of estradiol and raloxifene on collagen synthesis, by measuring the expression collagen I and III mRNA. STUDY DESIGN: Nineteen nulliparous young adult rhesus macaques underwent oophorectomy and were treated for 5 months with estradiol alone, raloxifene, or no hormone. Tissue samples were acquired from the lateral vaginal wall, and included the paravaginal attachment and levator ani muscle. Expression of mRNA for collagen I and III was measured by in situ hybridization. RESULTS: Estradiol increased mRNA for collagen I and III compared with no hormone and raloxifene treatment (ANOVA, P < .05). Collagen mRNA was localized to fibroblasts in the vaginal connective tissue and the connective tissue investments of striated muscle. Collagen mRNA was not expressed in epithelial, smooth, and striated muscle cells. CONCLUSION: Estrogen, but not raloxifene, increases collagen gene transcription and indicates stimulation of collagen synthesis in pelvic floor connective tissues.
Anatomic relationship between the vaginal apex and the bony architecture of the pelvis: a magnetic resonance imaging evaluation.
Gutman RE, Pannu HK, Cundiff GW, Melick CF, Siddique SA, Handa VL.
Am J Obstet Gynecol 2005 May;192(5):1544-8.
OBJECTIVE: This study was undertaken to define anatomic relationships between the vaginal apex and the ischial spines and sacrum for nulliparous women with normal support. STUDY DESIGN: We retrospectively evaluated the magnetic resonance images of 11 consecutive women who underwent pelvic imaging at Johns Hopkins. Coordinates were recorded for the posterior fornix, sacrum, ischial spines, and cervical vaginal junctions. We calculated vector distances with means, SDs, and 95% CIs. Intraclass correlation coefficients tested interobserver reliability and the Wilcoxon signed rank test compared right- and left-sided measurements. RESULTS: Mean age was 30.4 +/- 9.1 years. The cervical vaginal junction was 1.6 +/- 0.5 cm superior, 1.1 +/- 0.5 cm anterior, and 4.7 +/- 0.4 cm medial to the ipsilateral ischial spine. The posterior fornix was 1.0 +/- 1.0 cm anterior and 5.3 +/- 0.8 cm inferior to the second sacral vertebra. There was excellent interobserver reliability (interclass correlation coefficients = 0.997, P < .001) and no detectable difference between sides. CONCLUSION: Consistent relationships exist between the vaginal apex and ischial spines and sacrum, which may be useful in reconstructive pelvic surgery.
Does vaginal closure force differ in the supine and standing positions?
Morgan DM, Kaur G, Hsu Y, Fenner DE, Guire K, Miller J, Ashton-Miller JA, Delancey JO.
Am J Obstet Gynecol 2005 May;192(5):1722-8.
OBJECTIVE: This study was undertaken to quantify resting vaginal closure force (VCF(REST)), maximum vaginal closure force (VCF(MAX)), and augmentation of vaginal closure force augmentation (VCF(AUG)) when supine and standing and to determine whether the change in intra-abdominal pressure associated with change in posture accounts for differences in VCF. STUDY DESIGN: Thirty-nine asymptomatic, continent women were recruited to determine, when supine and standing, the vaginal closure force (eg, the force closing the vagina in the mid-sagittal plane) and bladder pressures at rest and at maximal voluntary contraction. VCF was measured with an instrumented vaginal speculum and bladder pressure was determined with a microtip catheter. VCF(REST) was the resting pelvic floor tone, and VCF(MAX) was the peak pelvic floor force during a maximal voluntary contraction. VCF(AUG) was the difference between VCF(MAX) and VCF(REST). T tests and Pearson correlation coefficients were used for analysis. RESULTS: VCF(REST) when supine was 3.6 +/- 0.8 N and when standing was 6.9 +/- 1.5 N--a 92% difference (P < .001). The VCF(MAX) when supine was 7.5 +/- 2.9 N and when standing was 10.1 +/- 2.4 N--a 35% difference (P < .001). Bladder pressure when supine (10.5 +/- 4.7 cm H2O) was significantly less (P < .001) than when standing (31.0 +/- 6.4 cm H2O). The differences in bladder pressure when either supine or standing did not correlate with the corresponding differences in VCF at rest or at maximal voluntary contraction. The supine VCF(AUG) of 3.9 +/- 2.7 N, was significantly greater than the standing VCF(AUG) of 3.3+/-1.9 N. CONCLUSION: With change in posture, vaginal closure force increases because of higher intra-abdominal pressure and greater resistance in the pelvic floor muscles.
Evaluation of the role of pudendal nerve integrity in female sexual function using noninvasive techniques.
Connell K, Guess MK, La Combe J, Wang A, Powers K, Lazarou G, Mikhail M.
Am J Obstet Gynecol 2005 May;192(5):1712-7.
OBJECTIVE: Using quantitative sensory testing and a validated questionnaire, we investigated the role of pudendal nerve integrity in sexual function among women. STUDY DESIGN: Participants completed the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). Vibratory and pressure thresholds were measured at the S2 dermatome reflecting pudendal nerve distribution. RESULTS: A total of 56 women enrolled; 29 (51.8%) were asymptomatic and 27 (48.2%) had 1 or more forms of female sexual dysfunction (total sexual dysfunction) including: desire disorder 16.1%, arousal disorder 26.8%, orgasmic disorder 25%, and pain disorder 12.5%. Age, parity, menopausal status, and body mass index were similar between groups. PISQ scores were lower in symptomatic subjects compared with controls (P < .001). Decreased tactile sensation was found at the clitoris for women with total sexual dysfunction, desire disorder, and arousal disorder. Women with arousal disorder also had decreased tactile sensation at the perineum. CONCLUSION: Pudendal nerve integrity may play a role in female sexual dysfunction.
The distance between the perceived and the actual arcus tendineus fascia pelvis during vaginal paravaginal repair. Claydon CS, Maccarone JL, Grody MH, Steinberg A, Oyama I, Holzberg AS, Caraballo R.
Am J Obstet Gynecol 2005 May;192(5):1707-11.
OBJECTIVE: This study was undertaken to determine whether the arcus tendineus fascia pelvis (ATFP) can be accurately identified from the paravaginal space (PVS) without entering the retropubic space (RPS). STUDY DESIGN: Eight patients undergoing vaginal paravaginal repair were enrolled. The paravaginal dissection was completed to the most cephalad portion of the PVS without entering the RPS. The apex of each PVS was stained with methylene blue. The RPS was entered, the ATFP visualized, and 4 sutures were placed along its length to be used for the repair. The perpendicular distance between each suture and the most cephalad area of stain was measured. RESULTS: The mean distance from the perceived to actual ATFP at each suture point (1-4) was 3.5 cm, 2.75 cm, 2.0 cm, and 0.91 cm, respectively. CONCLUSION: In these 8 cases, the RPS had to be entered to accurately identify the ATFP. The degree of error increases as the ischial spine is approached (P < .001).
The effects of hormone replacement on the biomechanical properties of the uterosacral and round ligaments in the monkey model.
Vardy MD, Gardner TR, Cosman F, Scotti RJ, Mikhail MS, Preiss-Bloom AO, Williams JK, Cline JM, Lindsay R.
Am J Obstet Gynecol 2005 May;192(5):1741-51.
OBJECTIVE: The purpose of this study was to determine effects of ovariectomy (OVX) and conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA), or ethinyl estradiol plus norethindrone acetate (EE/NA) on biomechanics of uterosacral (USL) and round (RL) ligaments in postmenopausal (PMP) monkeys. STUDY DESIGN: This was a randomized, triple blind, placebo-controlled study. OVX monkeys received 12 months no treatment (Pbo) (n = 19), CEE/MPA (n = 19), or EE/NA (n = 21). USL and RL step strains and stress-relaxation data were curve-fitted, giving strain-dependent tensile modulus (TM) from 0% to 30%. RESULTS: (1) USL: TM for both treatment groups was greater than Pbo for strains from 0% to 12% (P < .04). (2) RL: TM for both treatment groups was smaller than Pbo for strains from 12% to 30% (P < .05). No differences were found between treatment regimens. CONCLUSION: CEE/MPA and EE/NA both affect functional biomechanical properties by increasing tensile stiffness in the USL and decreasing it in the RL.
Clitoral anatomy in nulliparous, healthy, premenopausal volunteers using unenhanced magnetic resonance imaging.
O'Connell HE, DeLancey JO.
J Urol 2005 Jun;173(6):2060-3.
PURPOSE: We determined the magnetic resonance imaging (MRI) characteristics of normal clitoral anatomy. MATERIALS AND METHODS: A series of MRI studies of 10 healthy, nulliparous volunteers with no prior surgery and normal pelvic examination was studied and the key characteristics of clitoral anatomy were determined. A range of different magnetic resonance sequences was used without any contrast agent. RESULTS: The axial plane best revealed the clitoral body and its proximal continuation as the paired crura. The glans was seen more caudal than the body of the clitoris. The bulbs of the clitoris had the same signal as the rest of the clitoris in the axial plane and they related consistently to the other erectile structures. The bulbs, body and crura formed an erectile tissue cluster, namely the clitoris. In turn, the clitoris partially surrounded the urethra and vagina, forming a consistently observed tissue complex. Midline sagittal section revealed the shape of the body, although in this plane the rest of the clitoris was poorly displayed. The coronal plane revealed the relationship between the clitoral body and labia. The axial section cephalad to the clitoral body best revealed the vascular component of the neurovascular bundle to the clitoris. The fat saturation sequence particularly highlighted clitoral anatomy in healthy, premenopausal, nulliparous women. CONCLUSIONS: Normal clitoral anatomy has been clearly demonstrated using noncontrast pelvic MRI.
Cyclic adenosine monophosphate and cyclic guanosine monophosphate-phosphodiesterase isoenzymes in human vagina: relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide-containing nerves.
Uckert S, Oelke M, Waldkirch E, Stief CG, Albrecht K, Troger HD, Jonas U, Andersson KE, Hedlund P
Urology 2005 Mar;65(3):604-10.
OBJECTIVES: To evaluate the distribution of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) phosphodiesterases (PDEs) in relation to nitric oxide synthase isoforms and vasoactive intestinal polypeptide (VIP) in specimens of the human vagina. Nitric oxide and VIP, mediating biologic signals through cGMP and cAMP, have been assumed to be involved in the control of vaginal smooth muscle. METHODS: Immunohistochemical techniques were applied to sectioned specimens of the human vaginal wall to evaluate the presence of the PDE isoenzymes 3, 4, 5, and 10 in relation to neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and VIP. RESULTS: Immunoreactivity (IR) for cAMP-degrading PDE-4 was observed in the vaginal nonvascular smooth musculature, as well as in the wall of subepithelial arteries. VIP-IR nerves innervated the smooth muscle portion of the vaginal wall and also formed a subepithelial network. Immunoreactivity specific for PDE-5 was also registered in vascular and nonvascular vaginal smooth muscle. Immunosignals for eNOS were detected in the endothelial lining of arteries containing PDE-5-IR smooth muscle cells. These arteries were supplied by nNOS-IR nerve fibers. PDE-10-IR smooth muscle cells were located in muscle bundles of the vaginal wall. CONCLUSIONS: Our study revealed immunoreactivity specific for PDE-4, PDE-5, and PDE-10 in the vascular and nonvascular smooth muscle of the vagina. Immunosignals for PDE-4 and PDE-5 were also observed in close proximity to nNOS-IR or VIP-IR nerve fibers or to eNOS-IR endothelial cells. The distribution of PDEs may indicate a role of these enzymes in the control of the function of the human vagina.
Re: Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat.
Shafik A
J Urol 2005 Apr;173(4):1436; author reply 1436.
A rat model to study the structural properties of the vagina and its supportive tissues.
Moalli PA, Howden NS, Lowder JL, Navarro J, Debes KM, Abramowitch SD, Woo SL
Am J Obstet Gynecol 2005 Jan;192(1):80-8.
Objective The purpose of this study was to investigate the rat as a model for evaluating the structural properties of the vagina and its supportive tissues. Study design The in situ relationships between the vagina and its supportive tissues were studied grossly (n = 10), and in serial cross sections (n = 4). For biomechanical testing (n = 10), the lumbar spine was fixed to a testing machine while the distal vagina was gripped with a soft-tissue clamp mounted to a load-cell on the crosshead of the machine. The vagina was systematically pulled through the pelvis until failure of the supportive tissues occurred. Parameters describing the structural properties of the tissues (linear stiffness, ultimate load, ultimate elongation, and energy absorbed to failure) were determined from the resulting load-elongation curve. A coefficient of correlation (R) was used to determine experimental reproducibility. Results The rat vagina is supported by structures analogous to those in humans. The parameters describing the structural properties of these tissues were highly correlated among specimens ( R = 0.95). The mechanism of failure was similar for all specimens. Conclusion We have developed a mechanical testing protocol in which the structural properties of the vagina-supportive tissue complex can be measured. This will be a powerful tool for testing the impact of life events on vaginal support.