Effects of Pneumoperitoneum and the Steep Trendelenburg Position on Heart Rate Variability and Cerebral Oxygenation during Robotic Sacrocolpopexy.

STUDY OBJECTIVE: The aim of this study was to investigate how steep Trendelenburg positioning with pneumoperitoneum modifies brain oxygenation and autonomic nervous system modulation of heart rate variability during robotic sacrocolpopexy. DESIGN: Prospective study (Canadian Task Force classification III). SETTING: Rambam Health Care Campus. PATIENTS: Eighteen women who underwent robotic sacrocolpopexy for treatment of uterovaginal or vaginal apical prolapse. INTERVENTIONS: Robotic sacrocolpopexy. MEASUREMENTS AND MAIN RESULTS: A 5-minute computerized electrocardiogram, cerebral O2 saturation (cSO2), systemic O2 saturation, heart rate (HR), diastolic blood pressure (BP), systolic BP, and end-tidal CO2 tension were recorded immediately after anesthesia induction (baseline phase) and after alterations in positioning and in intra-abdominal pressure. HR variability was assessed in time and frequency domains. Cerebral oxygenation was measured by the technology of near-infrared spectrometry. cSO2 at baseline was 73% ± 9%, with minor and insignificant elevation during the operation. Mean HR decreased significantly when the steep Trendelenburg position was implemented (66 ± 10 vs 55 ± 9 bpm, p < .05) and returned gradually to baseline with advancement of the operation and the decrease in intra-abdominal pressure. Concomitant with this decrease, the power of both arms of the autonomic nervous system increased significantly (2.8 ± .8 vs 3.3 ± .9 ms2/Hz and 2.5 ± 1.2 vs 3.2 ± .9 ms2/Hz, respectively, p < .05). All these effects occurred without any significant shifts in systolic or diastolic BP or in systemic or cerebral oxygenation. CONCLUSION: This study supports the safety of robotic sacrocolpopexy performed with steep Trendelenburg positioning with pneumoperitoneum. Only minor alterations were observed in cerebral oxygenation and autonomic perturbations, which did not cause clinically significant alterations in HR rate and HR variability.

[Outcomes of ER:YAG LASER treatment of stress urinary incontinence in women].

AIM: To evaluate the effectiveness of a new method of treatment for stress urinary incontinence in women using an ER: YAG laser in SMOOTH mode and investigate pathophysiological and pathomorphological changes induced by erbium laser. MATERIALS AND METHODS: This study comprised 98 women aged 37-63 years, who between 2014 and 2016 were diagnosed with SUI (type 1 and 2a, 2b) and grade 0-2 vaginal prolapse. The treatment was performed with a 2940 nm Er:YAG laser (Fotona, Slovenia) using a SMOOTH mode. Clinical assessment included PFIQ-7 and PISQ-12 questionnaires, uroflowmetry, laser Doppler flowmetry and biopsy of the anterior vaginal wall. The examination was carried out at baseline and 1-2 months after the treatment. RESULTS: The effectiveness of treatment was 73%. There was no deterioration after the procedure. Analysis of PFIQ-7 and PISQ-12 questionnaires showed that patients with mild incontinence had the greatest difference between pre- and posttreatment results. Uroflowmetry parameters improved in a majority of patients. Results of laser Doppler flowmetry demonstrated the improvement of blood flow in the microvascular bed. An important feature of the vaginal biopsy after laser exposure was an increase in neoangiogenesis. DISCUSSION: The findings of questionnaires and clinical evaluation of patients with SUI and vaginal prolapse before and after treatment with Er: YAG laser showed high therapeutic effectiveness of this treatment modality. CONCLUSION: Clinical effectiveness of ER: YAG laser in SMOOTH mode was 73%. Patients with type 1 and 2a SUI and mild or moderate incontinence have the best prognosis after treatment with this method.

The expression of glutathione peroxidase-1 and the anabolism of collagen regulation pathway transforming growth factor-beta1-connective tissue growth factor in women with uterine prolapse and the clinic significance.

OBJECTIVES: To investigate the expression of the anabolism of collagen regulation pathways connective tissue growth factor (CTGF) -transforming growth factor-betal (TGF-beta1) and glutathione peroxidase-1 (GPx1) in women with uterine prolapse and a study of the clinic significance. MATERIALS AND METHODS: The expression of TGF-beta1, CTGF, and GPx1 was detected by immunohistochemical staining in pubocervical fascia tissue of 30 women with uterine prolapse, including ten cases of POP-QII, ten cases of POP-QIII, ten cases of POP-QIV, and 20 cases were control group with non-prolapse and non-malignant lesions. RESULTS: There was a negative correlation between the POP-Q and expression of TGF-beta1. With the increase of POP-Q degree, the expression degree of TGF-beta1 decreased correspondingly, which also applied to CTGF and GPx1. On the other hand, there was a positive correlation between TGF-beta1 and CTGF. The synergistic change trend was found between TGF-beta1 and CTGF. It could also be seen between CTGF and GPx1 and betweenTGF-beta1 and GPx1. CONCLUSION: The expression of the antioxidase GPx1 in pelvic support structure of POP women was decreased, which resulted in the antioxidation reduced. It could break the balance of oxidation and antioxidation in pelvic support structure, and may induce an increase of ROS level and the down-regulation of TGF-beta1-CTGF pathway. It could inhibit the anabolism of collagen and injury the pelvic support structure, thus promoting the occurrence and development of POP.

Relationship between the expression of fibulin-3 and anterior vaginal wall prolapse.

Anterior vaginal wall prolapse is the most common type of pelvic organ prolapse. Vaginal wall samples were obtained from women with (n =12) and without (n =12) anterior vaginal wall prolapse. No reports have been published on the content of fibulin-3 in the vaginal walls of patients with prolapse; thus, we compared the expression of fibulin-3 in the vaginal walls of women with and without anterior vaginal wall prolapse. RT-PCR was performed to measure mRNA expression and the expression of protein was assessed by immunohistochemistry. Statistical analysis was performed to determine differences between the two groups of women. Age, parity and menopausal status did not differ between women with and without prolapse. The expressions of fibulin-3 mRNA and protein were not different between the prolapse and no prolapse groups. It is unlikely that abnormal expression of fibulin-3 has a major role in the pathogenesis of anterior vaginal wall prolapse.

Role of fibulin-5 insufficiency and prolapse progression on murine vaginal biomechanical function.

The vagina plays a critical role in supporting the pelvic organs and loss of support leads to pelvic organ prolapse. It is unknown what microstructural changes influence prolapse progression nor how decreased elastic fibers contributes to vaginal remodeling and smooth muscle contractility. The objective for this study was to evaluate the effect of fibulin-5 haploinsufficiency, and deficiency with progressive prolapse on the biaxial contractile and biomechanical function of the murine vagina. Vaginas from wildtype (n = 13), haploinsufficient (n = 13), and deficient mice with grade 1 (n = 9) and grade 2 or 3 (n = 9) prolapse were explanted for biaxial contractile and biomechanical testing. Multiaxial histology (n = 3/group) evaluated elastic and collagen fiber microstructure. Western blotting quantified protein expression (n = 6/group). A one-way ANOVA or Kruskal-Wallis test evaluated statistical significance. Pearson's or Spearman's test determined correlations with prolapse grade. Axial contractility decreased with fibulin-5 deficiency and POP (p < 0.001), negatively correlated with prolapse grade (ρ = - 0.80; p < 0.001), and positively correlated with muscularis elastin area fraction (ρ = - 0.78; p = 0.004). Circumferential (ρ = 0.71; p < 0.001) and axial (ρ = 0.69; p < 0.001) vaginal wall stresses positively correlated with prolapse grade. These findings demonstrated that fibulin-5 deficiency and prolapse progression decreased vaginal contractility and increased vaginal wall stress. Future work is needed to better understand the processes that contribute to prolapse progression in order to guide diagnostic, preventative, and treatment strategies.

Failure of pelvic organ support in mice deficient in fibulin-3.

Fibulin-5 is crucial for normal elastic fiber synthesis in the vaginal wall; more than 90% of fibulin-5-knockout mice develop pelvic organ prolapse by 20 weeks of age. In contrast, fibulin-1 and -2 deficiencies do not result in similar pathologies, and fibulin-4-knockout mice die shortly after birth. EFEMP1 encodes fibulin-3, an extracellular matrix protein important in the maintenance of abdominal fascia. Herein, we evaluated the role of fibulin-3 in pelvic organ support. Pelvic organ support was impaired significantly in female Efemp1 knockout mice (Fbln3(-[supi]/-)), and overt vaginal, perineal, and rectal prolapse occurred in 26.9% of animals. Prolapse severity increased with age but not parity. Fibulin-5 was up-regulated in vaginal tissues from Fbln3(-[supi]/-) mice regardless of prolapse. Despite increased expression of fibulin-5 in the vaginal wall, pelvic organ support failure occurred in Fbln3(-[supi]/-) animals, suggesting that factors related to aging led to prolapse. Elastic fiber abnormalities in vaginal tissues from young Fbln3(-[supi]/-) mice progressed to severe elastic fiber disruption with age, and vaginal matrix metalloprotease activity was increased significantly in Fbln3(-[supi]/-) animals with prolapse compared with Fbln3(-[supi]/-) mice without prolapse. Overall, these results indicate that both fibulin-3 and -5 are important in maintaining pelvic organ support in mice. We suggest that increased vaginal protease activity and abnormal elastic fibers in the vaginal wall are important components in the pathogenesis of pelvic organ prolapse.

Differential expression of smooth muscle regulatory proteins in the uterosacral ligaments of women with uterine prolapse.

OBJECTIVE: To compare smooth muscle regulatory protein expression in the uterosacral ligament (USL) of women with and without uterine prolapse. STUDY DESIGN: USLs ligament were sampled in women with (n = 9) or without (n = 9) uterine prolapse. Caldesmon, smooth muscle actin (SMA), myosin heavy chain, and zinc finger protein messenger RNA expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine protein expression. RESULTS: Caldesmon messenger RNA expression and the ratio of caldesmon-SMA messenger RNA expression was significantly increased in the USL from women with uterine prolapse compared with women without prolapse (caldesmon mean +/- standard deviation messenger RNA, 0.81 +/- 0.46 vs 0.39 +/- 0.16; P = .01 and caldesmon-SMA messenger RNA ratio, mean +/- standard deviation, 0.11 +/- 0.04 vs 0.07 +/- 0.02; P = .01). In addition, the ratio of caldesmon-SMA staining was significantly increased in women with uterine prolapse compared with women without prolapse (mean +/- standard deviation, 0.44 +/- 0.28 vs 0.28 +/- 0.16; P = .03). CONCLUSION: Uterine prolapse is associated with an increased ratio of caldesmon-SMA actin expression.

Extracellular matrix expression of human prolapsed vaginal wall.

OBJECTIVE: To compare the mRNA expression of extracellular matrix (ECM) proteins in postmenopausal prolapsed versus non-prolapsed anterior vaginal wall (AVW) tissue. We hypothesized that the weakening of the tissue leading to prolapse was due to decreased collagen production from a downregulation at the transcriptional level. METHODS: Following IRB approval, full thickness samples of redundant AVW were excised from consecutive age-equivalent, postmenopausal, women undergoing cystocele repair (prolapse, stage III or IV), or radical cystectomy (control, no clinical findings of prolapse). Total RNA was isolated, cDNA was synthesized, and quantitative real-time polymerase chain reaction (PCR) was conducted to assess the mRNA expression of collagens type I and III, pro-elastin, MMP3, MMP10, and MMP11. The significance of the difference of mRNA expression between prolapse and control tissues was tested using Student's t-test followed by Mann-Whitney Rank Sum Test. RESULTS: A 5.3-fold increase in collagen type I mRNA was found in prolapse (n = 47) over control (n = 7) tissues (P = 0.009). Type III collagen mRNA was also significantly increased to a 3.3 times higher level (P = 0.017). The ratio of type III to type I was decreased from 15.6 in controls to 9.7 in prolapse. An increasing trend in pro-elastin and MMP mRNA expression was found in prolapse, but this was not statistically significant. CONCLUSION: In this controlled study, the increase found in collagen mRNA expression disproved our hypothesis. To the contrary, this defective prolapsed tissue can signal its need for ECM replenishment. The message, however, is not being effectively translated to assist in tissue remodeling.

Differential expression of fibulins in the uterosacral ligaments of women with uterine prolapse.

PURPOSE: To compare fibulin-3 (FIB-3) and fibulin-5 (FIB-5) expressions in uterosacral ligaments (USL) of women with and without uterine prolapse. STUDY DESIGN: USL were sampled in a standardized fashion from women with (n = 8) or without (n = 8) uterine prolapse. Quantitative Real-Time PCR was performed to measure mRNA and immunohistochemistry to assess protein expression. RESULTS: FIB-3 mRNA expression and FIB-3 staining intensity was similar in the USL of women with and without uterine prolapse {[(FIB-3 mean +/- SD mRNA relative units) 0.45 +/- 0.41 vs. 0.46 +/- 0.82, NS] and [Intensity score, median (range), 1(0-1) vs. 1(0-1), NS]}. Both FIB-5 mRNA expression and FIB-5 staining intensity was significantly decreased in USL from women with uterine prolapse compared to women without prolapse {[(FIB-5 mean +/- SD mRNA relative units) 0.07 +/- 0.02 vs. 0.26 +/- 0.20, P = 0.02] and [Intensity score, median (range), 0(0-2) vs. 3(2-3), P = 0.002]}. CONCLUSION: FIB-5 expression is decreased in USL of women with uterine prolapse.

[Microarray analysis of gene expression profiles in pelvic organ prolapse].

OBJECTIVE: To identify the differentially expressed genes in cardinal ligament between patients with pelvic organ prolapse (POP) and postmenopausal women without POP by Human Genome Expression Chip and explore the potential molecular mechanism involved in POP. METHODS: From January to May, 2007, cardinal ligament samples were obtained from 3 postmenopausal patients with POP-Q stage III and 3 postmenopausal patients underwent hysterectomy due to other benign gynecologic diseases without POP in Peking Union Medical College Hospital. HE and Masson's trichrome staining was used to verify tissue origin and inspect histological changes. Those differentially expressed genes in cardinal ligaments were identified by Human Genome Chip and further interrogated with Gene Ontology (GO) and Pathway Analysis. Those remarkable expressed genes were confirmed by qRT-PCR. RESULTS: Alterations of ligament architecture in POP patients included disarrangement and collapse of smooth muscle bundles and collagen fibers. A total of 179 differentially expressed genes were screened between POP and non-POP cardinal ligament tissue, including 20 functional unknown genes. A total of 107 genes were upregulated in POP group, while 72 genes downregulated. Those differentially genes were revealed associated with multiple functional proteins and metabolic pathways by biological analysis. Among these, Wnt signaling pathway exhibited the most remarkable changes. Real-time quantitative PCR showed the genes of COL1A1, DKK1, SFRP1, FZD5, WNT16b in POP group (2.98+/-1.40, 3.03+/-0.48, 8.13+/-4.42, 5.19+/-3.50, 12.40+/-3.88) were upregulated significantly compared with non-POP group (1.09+/-0.08, 1.20+/-0.18, 0.41+/-0.51, 0.87+/-0.24, 1.40+/-0.47; P<0.05). CONCLUSIONS: The pathophysiology of POP is complex and associated with multiple functional proteins and metabolic pathways. Among these, the antagonist DKK1, SFRP1 in Wnt signaling pathway may contribute to a neurodegenerative role in POP development.

Metastatic Acinic Cell Carcinoma to the Vagina: A First Reported Case.

This is a case of a 62-year-old woman with a remote history of acinic cell carcinoma of the parotid gland, who presented with a palpable vaginal mass, anterior vaginal wall prolapse, and stress urinary incontinence. A 2 cm firm mobile mass on the anterior vaginal wall was found on clinical examination. A computed tomographic scan revealed a mass between the vaginal vault and bladder that was eventually surgically excised. The histology, supported by the immunohistochemistry, revealed metastatic acinic cell carcinoma to the vagina after 37 years of her initial diagnosis. This is the first reported case in the literature to occur in the vagina.

Markers of collagen synthesis and degradation in urogenital tissue and serum from women with and without uterovaginal prolapse.

Diverging results have been published concerning collagen metabolism in uterovaginal prolapse (UP). We have investigated collagen turnover in urogenital tissue in urologically healthy women with (UP patients) and without UP or any history of UP (controls). Markers of collagen turnover, carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of procollagen III (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were assayed in urogenital tissue homogenates and serum. Tissue and serum concentrations of collagen turnover markers were related to UP and to menopausal/estrogen status. UP patients were significantly older than the controls. UP patients had significantly higher tissue PICP and PIIINP and significantly lower tissue ICTP levels than the controls, but the difference in ICTP disappeared after matching for menopausal/estrogen status and age. There were no associations between tissue collagen turnover markers on the one hand and menopausal/estrogen status or age on the other. The higher tissue concentrations of PICP and especially PIIINP in tissue from women with UP compared to controls, suggest an increased collagen breakdown in UP. This pattern differs from that in stress urinary incontinent women without UP, where tissue levels of collagen turnover markers are low, indicating reduced collagen breakdown.

High isoprostane level in cardinal ligament-derived fibroblasts and urine sample of women with uterine prolapse.

We studied the isoprostane level, a well-recognised biomarker of oxidative stress, from women with uterine prolapse and age-matched female controls without prolapse. Cardinal ligament-derived fibroblasts explanted from women with prolapse showed a significant increased level of isoprostane production (P < 0.05) compared with those derived from controls. This concurs with elevated urinary isoprostane levels identified among women with prolapse (P < 0.001) compared with controls. In addition, the matrix metalloproteinase 2 mRNA was significantly increased (P= 0.004) among women with uterine prolapse. Parallel findings of increased isoprostane in cardinal ligament and urine sample among women with prolapse suggest that oxidative stress might be involved in the development of uterine prolapse.

Quantitative analysis of 17 amino acids in the connective tissue of patients with pelvic organ prolapse using capillary electrophoresis-tandem mass spectrometry.

The simultaneous determination of 17 amino acids in connective tissue using capillary electrophoresis is described in this study. Separation was carried out on a fused silica capillary column (80 cm x 50 mm i.d.) with 1M formic acid as the running electrolyte. The detection was conducted on a mass spectrometer by selective reaction monitoring (SRM) mode via an electrospray ionization source. Tissue samples were prepared by reduction and acid hydrolysis to extract amino acids; over 84.3% recovery was seen for all compounds. The method allowed for sensitive, reproducible, and reliable quantification, and all 17 amino acids were separated using this method. Good linearity over the investigated concentration ranges was observed, with values of R higher than 0.993 for all the analytes. Precision and accuracy examined at three concentration levels ranged from 0.2% to 19.5% and 84.1% to 120.0%, respectively. Matrix effects were also tested and ranged from -9.1% to 15.4%. The validated method was applied to the quantitation of 17 amino acids in pelvic connective tissue of pelvic organ prolapsed patients. Methionine, glutamine, and histidine were significantly higher in the experimental patients compared to the controls. This suggests that changes in the amino acid concentrations within the connective tissue could be a factor in the genesis of pelvic organ prolapse. Therefore, this method is potentially applicable for amino acid analysis in tissue, providing a more complete understanding of pelvic organ prolapse.

Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.

Decreased endopelvic fascia elastin content in uterine prolapse.

BACKGROUND: Genital prolapse is a debilitating manifestation of pelvic floor dysfunction. The cause of this condition has not been elucidated. The purpose of this study was to determine elastin content and RNA expression of related enzymes of elastin synthesis in uterosacral ligament biopsies from women with severe prolapse, and controls with normal pelvic support. METHODS: Biopsies were taken from the uterosacral ligament tissue of 31 women with Grade III or greater prolapse and 29 women with normal pelvic support. Elastin content was assessed by measuring desmosine using radioimmunoassay, and quantitative real time PCR was performed to quantify mRNA levels of lysyl oxidase (LOX), lysyl oxidase like-1 (LOXL1), LOXL2 and fibulin-5 (FIB-5). RESULTS: The mean desmosine concentration found in uterosacral ligaments of women with prolapse (n =26) was 103.3+/-59.3 pmolD/mgP compared to controls (n =29) 120.5+/-47.4 pmolD/mgP (p =0.1943). In the subgroup of subjects with complete procidentia (n =8), mean desmosine concentration was 50.6+/-25.8 and 127.1+/-42.2 pmolD/mgP in age-matched controls (n =12) (p <0.05). In tissue from subjects with more than 2 vaginal deliveries (n =18), the mean desmosine concentration was 99.9+/-60.7 and 133.0+/-44.0 pmolD/mgP in controls (n =17) (p <0.05). Expression of LOX, LOXL1 and LOXL2 decreased 8.2-fold+/-3.4, 5.0-fold+/-1.7 and 15.2-fold+/-5.2, respectively (mean+/-SD) in cases versus controls (p<0.05). Expression of FIB-5 was increased 3.1-fold+/-0.7 compared to controls (p<0.05). CONCLUSIONS: Significantly decreased desmosine content was measured in the uterosacral ligament tissue from women with prolapse versus controls in women with parity >2 and in women with complete procidentia. Suppression of mRNA for LOX and two LOX isoenzymes was correspondingly present. These results suggest that altered elastin metabolism is present in women with uterine prolapse.

Differential elastin and tenascin immunolabeling in the uterosacral ligaments in postmenopausal women with and without pelvic organ prolapse.

Connective tissue, consisting mainly of collagen and structural glycoproteins, is an important part of the supportive structures of the genitourinary region. Relatively few data have been published with respect to the role of elastin and glycoproteins in pelvic organ prolapse (POP). Connective tissue of the uterosacral ligament in postmenopausal women with and without genital prolapse was compared. Fifty-nine consecutive women referred for hysterectomy were included in the study. The patients had POP or benign gynecological disease (e.g. myoma of the uterus). Tissue samples from the uterosacral ligament were investigated for localization and distribution of tenascin and elastin using immunofluorescence microscopy. Tissue samples of women with prolapse showed a significantly (p<0.001) weaker immunofluorescent labeling of tenascin compared to samples taken from women without prolapse. Tenascin was detectable in tissues of all women with POP, whereas its immunolabeling was decreased in the uterosacral ligament in women without POP. Intact elastin fibers were observed in tissues of all women without POP, whereas elastin was undetectable or sometimes fragmented in the uterosacral ligament in women with POP. Greater amounts of tenascin and lesser amounts of elastin were therefore found in patients with POP. These results suggest that an altered turnover of connective tissue in the uterosacral ligament might be responsible for the presence of pelvic floor relaxation in postmenopausal women. These data indicate a complex architecture of the extracellular matrix in the uterosacral ligaments, with marked differences in tenascin and elastin expression between postmenopausal women with or without POP.

Neuropeptide Y expression in vaginal epithelium of women with pelvic organ prolapse and stress urinary incontinence.

OBJECTIVES: To determine the role of neuropeptide Y (NPY) in anterior and posterior vaginal epithelium in the etiologic development of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). METHODS: Forty biopsy specimens from anterior and posterior vaginal epithelium were obtained from 40 POP/SUI patients and controls. The specimens were stained using hematoxylin and eosin and NPY immunohistochemical staining. NPY was measured semiquantitatively and NPY mRNA expression was assessed using DNA hybridization in situ. RESULTS: There were no significant differences in NPY between anterior and posterior vaginal epithelium. NPY profiles in posterior vaginal epithelium in the SUI group were significantly lower than in the POP (P<0.05) and control (P<0.05) groups. In the POP group, the NPY profile correlated negatively with advancing age and years post menopause. CONCLUSION: The reduction in NPY in the anterior and posterior vaginal wall epithelium might be related to nerve damage or degeneration, resulting in a change in blood flow, atrophy, and pelvic floor laxity in patients with POP and SUI, especially post menopause and with advancing age.

[Expression of androgen receptor in the vaginal wall and cardinal ligament of patients with pelvic organ prolapse].

OBJECTIVE: To evaluate the role of androgen and its receptor in the pathogenesis of prolapse of pelvic floor. METHODS: Specimens of right cardinal ligament and vaginal wall were collected from 38 patients with prolapse, aged (64 +/- 3) (45 - 79), all menopausal, and 23 women, aged (50 +/- 2)(45-57), with obstetric or gynecologic diseases other than prolapse (as controls), all undergoing total hysterectomy. The 38 prolapse patients were divided into 2 groups: Group > or = 60, aged (66 +/- 6), and Group < 60, aged (52 +/- 5). Western blotting and immunohistochemistry were used to detect the expression of androgen receptor (AR) in the tissues. Peripheral blood samples were collected from all patients to examine the levels of serum testosterone and sex hormone binding globulin (SHBG) by chemiluminescent labeling. RESULTS: There were no significant differences in the serum concentrations of testosterone and SHBG between the prolapse and the control groups. The AR positive rates in the cardinal ligament and vaginal wall tissues of the prolapse patients aged > or = 60 were (49 +/- 15)% and (49 +/- 10)% respectively, both not significantly different from those of the control group [(43 +/- 15)% and (42 +/- 3)% respectively, both P > 0.05]. ears, The AR expression rates in the tissues of cardinal ligament and vaginal wall of the prolapse patients were (42 +/- 3)% and (43 +/- 15)% respectively, both significantly higher than those of the control group [(29 +/- 7)% and (29 +/- 6)% respectively, both P < 0.001]. Western blotting showed that the positive rate of the AR with the relative molecular weight of 45 000 in the cardinal ligament of the prolapse group was 4.41%, significantly higher than that of the control group (2.1%, P = 0.02), however, the positive rate of the AR with the relative molecular weight of 45 000 in the vaginal wall tissue of the prolapse group was 3.34%, not significantly different from that of the control group (2.28%, P = 0.2). There were no significant differences in the in the straps of 110 000 and 90 000 detected by C-terminal polyantibodies of AR in the cardinal ligament and vaginal wall tissues between the prolapse patients and the control group (both P > 0.05). CONCLUSION: The increasing expression of AR in the tissue of vaginal wall and cardinal ligament of the prolapse patients with pelvic floor dysfunction may play an important role in the etiology of pelvic floor dysfunction.

[Changes of collagen content in uterine ligaments of perimenopausal women with relaxation of pelvic supports].

OBJECTIVE: To investigate the changes in histological characteristics and collagen content in uterosacral and cardinal ligaments of perimenopausal women in relation to relaxation of pelvic supports. METHODS: Twenty-eight subjects undergoing hysterectomies were selected, in which 14 cases were perimenopausal women with relaxation of pelvic support as the relaxation group and 14 women at perimenopausal age with leomyoma, cervical cancer, adenomyosis as the control group. Samples of cardinal ligaments and uterosacral ligaments were obtained at hysterectomies, and the tissues were sliced and stained by Masson's trichrome technique. Histological characteristics of the samples were studied and immunohistochemistry assay was applied to demonstrate the contents of collagen types I and III. RESULTS: (1) The collagen in uterosacral ligaments and cardinal ligaments were stained blue by the Masson's trichome technique. In comparison to the control group, the relaxation group had milder positive stains of the collagen and the stains were distributed in unequal intensities. Collagen content was arranged in loose pattern. Focal arrangement of the collagen was dense but fragmented. Collagen fibers were atrophic. (2) In immunohistochemistry assay and image analysis, collagen was positive in light to deep brown areas. In the relaxation group, positive units of collagen types I and III in cardinal ligaments were 13.8 +/- 2.1 and 9.6 +/- 2.4 respectively. Positive units of collagen types I and III of cardinal ligaments in the control group were 27.4 +/- 3.5 and 17.7 +/- 4.0 respectively. Differences between these two groups were statistically significant (P<0.01). In the relaxation group, positive units of collagen types I and III in utero-sacral ligaments were 15. 8 +/- 2.5 and 10.3 +/- 3.6 respectively. Positive units of collagen types I and III of utero-sacral ligaments of the control group were 29.5 +/- 4.4 and 19.3 +/- 4.6 respectively. Differences between these two groups were statistically significant (P<0.01). CONCLUSIONS: Reductions in collagen types I and III occur in pelvic floor tissue of perimenopausal patients who suffer from pelvic support relaxation. Atrophic and degenerative changes of collagen fibers may be the basic pathological structural alteration in pelvic floor.