elastin and Uterine-Prolapse

The use of wide pore lightweight polypropylene mesh to improve anatomical outcomes in the surgical repair of prolapse has been hampered by mesh complications. One of the prototype prolapse meshes has been found to negatively impact the vagina by inducing a decrease in smooth muscle volume and contractility and the degradation of key structural proteins (collagen and elastin), resulting in vaginal degeneration. Recently, bioscaffolds derived from extracellular matrix have been used to mediate tissue regeneration and have been widely adopted in tissue engineering applications.. Here we aimed to: (1) define whether augmentation of a polypropylene prolapse mesh with an extracellular matrix regenerative graft in a primate sacrocolpopexy model could mitigate the degenerative changes; and (2) determine the impact of the extracellular matrix graft on vagina when implanted alone.. A polypropylene-extracellular matrix composite graft (n = 9) and a 6-layered extracellular matrix graft alone (n = 8) were implanted in 17 middle-aged parous rhesus macaques via sacrocolpopexy and compared to historical data obtained from sham (n = 12) and the polypropylene mesh (n = 12) implanted by the same method. Vaginal function was measured in passive (ball-burst test) and active (smooth muscle contractility) mechanical tests. Vaginal histomorphologic/biochemical assessments included hematoxylin-eosin and trichrome staining, immunofluorescent labeling of α-smooth muscle actin and apoptotic cells, measurement of total collagen, collagen subtypes (ratio III/I), mature elastin, and sulfated glycosaminoglycans. Statistical analyses included 1-way analysis of variance, Kruskal-Wallis, and appropriate post-hoc tests.. The host inflammatory response in the composite mesh-implanted vagina was reduced compared to that following implantation with the polypropylene mesh alone. The increase in apoptotic cells observed with the polypropylene mesh was blunted in the composite (overall P < .001). Passive mechanical testing showed inferior parameters for both polypropylene mesh alone and the composite compared to sham whereas the contractility and thickness of smooth muscle layer in the composite were improved with a value similar to sham, which was distinct from the decreases observed with polypropylene mesh alone. Biochemically, the composite had similar mature elastin content, sulfated glycosaminoglycan content, and collagen subtype III/I ratio but lower total collagen content when compared to sham (P = .011). Multilayered extracellular matrix graft alone showed overall comparable values to sham in aspects of the biomechanical, histomorphologic, or biochemical endpoints of the vagina. The increased collagen subtype ratio III/I with the extracellular matrix graft alone (P = .033 compared to sham) is consistent with an ongoing active remodeling response.. Mesh augmentation with a regenerative extracellular matrix graft attenuated the negative impact of polypropylene mesh on the vagina. Application of the extracellular matrix graft alone had no measurable negative effects suggesting that the benefits of this extracellular matrix graft occur when used without a permanent material. Future studies will focus on understanding mechanisms.

Topics: Actins; Animals; Apoptosis; Biocompatible Materials; Collagen Type I; Collagen Type III; Elastin; Extracellular Matrix; Female; Glycosaminoglycans; Guided Tissue Regeneration; Macaca mulatta; Polypropylenes; Surgical Mesh; Tissue Scaffolds; Uterine Prolapse; Vagina

The pathophysiology of prolapse is not well understood. However, two main theories predominate: either the fibromuscular layer of the vagina develops a defect/tears away from its supports, or its tissues are stretched and attenuated. The aim of this study was to assess how vaginal wall thickness (VWT) is related to vaginal prolapse.. The study group comprised 243 women with symptomatic prolapse recruited from the Outpatient Department of a tertiary referral centre for urogynaecology. A history was taken and women were examined to determine their POP-Q score. Using a previously validated technique, ultrasonography was used to measure the mean VWT at three anatomical sites on the anterior and posterior walls. Scores were then compared using t tests, the Kruskal-Wallis test and the Friedman test.. The mean age of the patients was 59.7 years (SD 12.0 years range 38 - 84 years). For each measurement VWT reduced as prolapse grade increased until the prolapse extended beyond the hymen. Women with grade 3 prolapse had a significantly higher mean VWT than women with grade 1 or 2 contained prolapse. Menopause status did not have a significant effect on the VWT.. VWT is lower in women with vaginal prolapse until the prolapse extends beyond the hymen and then VWT is thicker and comparable with women without prolapse. This may be explained by changes in the vaginal tissue including reduction of collagen, elastin and smooth muscle, as well as fibrosis in exposed tissues, rather than by defects in the vagina.

Topics: Adult; Aged; Aged, 80 and over; Collagen; Elastin; Female; Humans; Middle Aged; Muscle, Smooth; Severity of Illness Index; Ultrasonography; Uterine Prolapse; Vagina

The impact of polypropylene mesh implantation on vaginal collagen and elastin metabolism was analyzed using a nonhuman primate model to further delineate the mechanism of mesh induced complications.. Forty-nine middle-aged parous rhesus macaques underwent surgical implantation of 3 synthetic meshes via sacrocolpopexy. Gynemesh PS (n = 12) (Ethicon, Somerville, NJ) and 2 lower-weight, higher-porosity, lower-stiffness meshes (UltraPro [n = 19] [Ethicon] and Restorelle [n = 8] [Coloplast, Minneapolis, MN]) were implanted, in which UltraPro was implanted with its blue orientation lines perpendicular (low stiffness direction, n = 11) and parallel (high stiffness direction, n = 8) to the longitudinal axis of the vagina. Sham-operated animals were used as controls (n = 10). Twelve weeks after surgery, the mesh-tissue complex was excised and analyzed.. Relative to sham, Gynemesh PS had a negative impact on the metabolism of both collagen and elastin-favoring catabolic reactions, whereas UltraPro induced an increase only in elastin degradation. Restorelle had the least impact. As compared with sham, the degradation of collagen and elastin in the vagina implanted with Gynemesh PS was increased with a simultaneous increase in active matrix metalloproteinase (MMP)-1, -8, -13, and total MMP-2 and -9 (all P < .05). The degradation of elastin (tropoelastin and mature elastin) was increased in the UltraPro-implanted vagina with a concomitant increase of MMP-2, and -9 (all P < .05). Collagen subtype ratio III/I was increased in Gynemesh PS and UltraPro perpendicular groups (P < .05).. Following implantation with the heavier, less porous, and stiffer mesh, Gynemesh PS, the degradation of vaginal collagen and elastin exceeded synthesis, most likely as a result of increased activity of MMPs, resulting in a structurally compromised tissue.

Topics: Animals; Blotting, Western; Collagen; Collagen Type I; Collagen Type III; Elastin; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Female; Macaca mulatta; Matrix Metalloproteinase 1; Matrix Metalloproteinase 13; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Polypropylenes; Procollagen; Surgical Mesh; Tropoelastin; Uterine Prolapse; Vagina

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.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Collagen Type I; Collagen Type III; Elastin; Extracellular Matrix Proteins; Female; Humans; Matrix Metalloproteinase 10; Matrix Metalloproteinase 11; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterine Prolapse; Vagina

To compare elastin metabolism in the vagina of women with and without pelvic organ prolapse and to define the regulation of this process by hormone therapy (HT).. Eighty-seven histologically confirmed full-thickness vaginal biopsies were procured from study participants at time of surgery. Premenopausal women with no prolapse served as controls. Women with prolapse were divided into three groups: premenopausal, postmenopausal not on HT, and postmenopausal on HT. The epithelium was excised leaving the subepithelium, muscularis, and adventitia for analyses. The elastin precursor, tropoelastin, was measured by immunoblotting and mature elastin protein via a desmosine cross-link radioimmunoassay. Matrix metalloproteinases (MMPs)-2 and -9 were quantitated by gelatin zymography. Data were analyzed using Kruskal-Wallis test and post hoc analysis using the Mann-Whitney U test.. Tropoelastin (432%), mature elastin (55%), proMMP-9 (90%), and active MMP-9 (106%) were increased in women with prolapse relative to those in the control group while active MMP-2 (41%) was decreased. Comparison of tropoelastin and mature elastin values obtained from the same women showed them to be independently regulated (r=0.19). Interestingly, the highest amount of both proteins occurred in postmenopausal patients not on HT.. Elastin metabolism is altered in the vagina of women with prolapse relative to those in the control group, suggesting that vaginal tissue is rapidly remodeling in response to mechanical stretch. We found that elastin levels are highest in the absence of hormones.

Topics: Adult; Elastin; Female; Humans; Immunoblotting; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Tropoelastin; Uterine Prolapse; Vagina; Young Adult

Pelvic organ prolapse is associated with defects in connective tissue including elastic fibers. The purpose of this study was to investigate expression of fibulin-5 and lysyl oxidase-like 1, which play an essential role in synthesis and assembly of elastic fibers in the uterosacral ligament, in samples taken from women with advanced pelvic organ prolapse compared with controls.. Specimens were obtained prospectively during abdominal hysterectomy from 30 women with advanced pelvic organ prolapse and 30 controls matched to the study group for age and parity among postmenopausal women with benign gynecologic pathology. Expression levels of protein and mRNA of fibulin-5 and lysyl oxidase-like 1 in uterosacral ligaments were measured by Western blot analysis and real-time quantitative polymerase chain reactions. For statistical analyses, Student's t-test, chi-square test, Mann-Whitney U test, Fisher's exact test and Spearman's correlation were used.. Significant decrease in the expression of mRNA of fibulin-5 was found in patients with prolapse (P-value=0.042; 0.743+/-0.229 and 1.061+/-0.537). The expression of mRNA of lysyl oxidase-like 1 was increased in the patient group (P-value=0.017; 4.099+/-2.832 and 1.816+/-1.602). Similar results were shown in Western blot analysis. Differences in expression of fibulin-5 and lysyl oxidase-like 1 were noted according to stage of prolapse (P-value=0.037 and 0.009).. There was decreased expression of fibulin-5 and increased expression of lysyl oxidase-like 1 in uterosacral ligaments in patients with pelvic organ prolapse, which suggests the possibility of defects in elastin synthesis.

Topics: Aged; Amino Acid Oxidoreductases; Case-Control Studies; Connective Tissue; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Female; Humans; Korea; Ligaments; Middle Aged; Prospective Studies; RNA, Messenger; Uterine Prolapse

To investigate expression of elastin, lysyl oxidase (LOX) and elafin in cardinal ligament of women with pelvic organ prolapse (POP) so as to determine their contributions to POP.. The cardinal ligament samples were obtained from 60 POP subjects and 60 non-POP control women undergoing hysterectomy. RT-PCR was used to verify the mRNA level of elastin, LOX and elafin. The protein concentration of the three genes was determined by western blotting technique, electrophoretic separation and quantification.. The premenopausal and postmenopausal POP groups demonstrated significantly decreased expressions of elastin in cardinal ligament both in mRNA and protein levels than control group (mRNA 0.42 +/- 0.22, 0.26 +/- 0.20 versus 0.79 +/- 0.30, 0.63 +/- 0.23; protein 0.44 +/- 0.32, 0.20 +/- 0.19 versus 0.89 +/- 0.27, 0.78 +/- 0.25; P < 0.05). There was an identical tendency in the expression of LOX (mRNA 0.37 +/- 0.18, 0.20 +/- 0.14 versus 0.65 +/- 0.22, 0.53 +/- 0.20; protein 0.45 +/- 0.27, 0.26 +/- 0.21 versus 0.85 +/- 0.39, 0.69 +/- 0.31; P < 0.05). In POP group, the mRNA and protein levels of elastin and LOX in postmenopausal patients were significantly lower than premenopausal patients (P < 0.05). Inversely, POP group demonstrated an increased expression of elafin in cardinal ligament both in mRNA and protein levels than corresponding control group (mRNA 1.33 +/- 0.35, 1.47 +/- 0.37 versus 0.62 +/- 0.25, 0.55 +/- 0.24; protein 0.85 +/- 0.30, 0.76 +/- 0.35 versus 0.21 +/- 0.15, 0.29 +/- 0.22; P < 0.05). There was no significant difference in the expression of elafin between premenopausal and postmenopausal POP groups either in mRNA or protein levels (P > 0.05). There was a positive correlation between elastin and LOX both in mRNA and protein levels in POP group(r = 0.9959, 0.9708; P < 0.05), but there was no correlation between elastin and elafin (r = -0.0402, -0.0365; P > 0.05).. The results suggest that the decreased expression of elastin and LOX and the increased expression of elafin in the cardinal ligaments may contribute to POP.

Topics: Adult; Aged; Case-Control Studies; Elafin; Elastin; Female; Gene Expression; Humans; Hysterectomy; Ligaments; Middle Aged; Postmenopause; Premenopause; Protein-Lysine 6-Oxidase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterine Prolapse; Uterus

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.

Topics: Aged; Aged, 80 and over; Collagen; Connective Tissue; Elastin; Female; Glycoproteins; Humans; Immunohistochemistry; Ligaments; Microscopy, Fluorescence; Middle Aged; Myoma; Pelvic Floor; Postmenopause; Sacrum; Tenascin; Uterine Prolapse; Uterus

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.. 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).. 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).. 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.

Topics: Adult; Aged; Biopsy; Desmosine; Elastin; Extracellular Matrix Proteins; Fascia; Female; Gene Expression; Humans; Isoenzymes; Ligaments; Middle Aged; Pelvic Bones; Protein-Lysine 6-Oxidase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterine Prolapse

Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.

Topics: Amino Acid Oxidoreductases; Animals; Disease Models, Animal; Elastin; Female; Homeostasis; Magnetic Resonance Imaging; Mice; Mice, Knockout; Pelvic Floor; Phenotype; Urethra; Urinary Bladder; Urinary Incontinence; Urogenital System; Uterine Prolapse

Solidity and elasticity are the two main biomechanical properties of pelvic tissues involved in surgical cure of genital prolapse-prevertebral, pectinate, and sacrospinal ligaments, tendinous arcs of the pelvic fascia, vaginal tissue. We report data in the literature and personal studies concerning these autologous biological tissues.. The resistance of pelvic tissues was tested on 29 cadavers. Measurements were also made on two 2-cm samples of vaginal tissue obtained during vaginal route surgery for prolapse cure in 20 menopaused women. Stress tests were conducted to determine resistance and level of rupture.. There was a wide variability in ligament resistance, ranging from a minimum of 22 Newtons to a maximum to the order of 200 Newtons. Results varied greatly from one woman to another and also between the two sides in the same woman. The prevertebral ligament exhibited the greatest resistance. The pectinate ligament was significantly more resistant than the sacrospinal ligaments and the tendinous arcs of the pelvic fascia. There was a significant relationship between the subjective assessment of ligament quality and objective measurements of resistance. For vaginal tissues, resistance varied greatly from 12 Newtons to a maximum to the order of 76 Newtons. Flexion values ranged from 14 to 130 Newtons.. Our findings illustrate pelvic tissue failure observed in patients with genital prolapse. Individual maximal resistance of the pelvic ligaments is vary variable, between ligaments and between subjects, and even between sides in a given subject. Pelvic ligaments used for cure of genital prolapse are moderately resistant with wide interindividual variability. The mechanical properties of vaginal tissue are also very variable, illustrating why these tissues may exhibit a certain resistance against dissociation when exposed to loading but much less resistance when exposed to traction by a surgical suture. These findings suggest a revision of classical surgical procedures.

Topics: Age Factors; Aged; Biomechanical Phenomena; Cadaver; Cicatrix; Collagen; Elasticity; Elastin; Fascia; Female; Humans; Ligaments; Middle Aged; Patient Selection; Prostheses and Implants; Stress, Mechanical; Sutures; Uterine Prolapse; Vagina

The precise mechanism of uterine prolapse is poorly understood. There is evidence to suggest that abnormalities of connective tissue structure or its repair mechanism may predispose women to prolapse.. This immunohistochemical study was performed on paraffin-embedded sections of the cardinal ligaments in an attempt to evaluate differences in the expression of extracellular matrix (ECM) proteins: collagen I, collagen III, elastin and tenascin, in the cardinal ligaments of prolapsed compared to non-prolapsed uteri. There appear to be discernable differences in the level of expression of ECM proteins in prolapsed compared to non-prolapsed cardinal ligaments. We found that the ligaments of the prolapsed uteri are characterized by a higher expression of collagen III and tenascin, and lower quantities of elastin. It appears that the use of HRT in post-menopausal women reverses some of the changes observed in cases of prolapse. Collagen I expression is directly related to the age and menopausal status rather than to prolapse.. In contrast to collagen I, our findings clearly indicate that collagen III expression is directly related to the presence of prolapse rather than age or menopausal status and is suppressed with the use of HRT. The pattern of change may fit a picture of healing phase of traumatized tissue as evidenced by the raised tenascin expression. The trauma itself may have been initiated by events such as childbirth, and that the lack of estrogen following the menopause results in decompensation. In spite of ameliorating some of the changes such as suppression of collagen III expression, treatment with estrogen falls short of rectifying the expression of other necessary proteins. If these mechanisms can be elucidated, a supplementary drug therapy may help along with estrogens to rebuild these ligaments.

Topics: Adult; Aged; Case-Control Studies; Collagen Type I; Collagen Type III; Elastin; Extracellular Matrix Proteins; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Ligaments; Middle Aged; Postmenopause; Tenascin; Uterine Prolapse

This study aimed to compare connective tissue components within the uterine ligaments histopathologically in women with and without pelvic relaxation. The tissue samples obtained from the histopathologic specimens of 24 patients with uterine descensus who underwent vaginal hysterectomy and from twenty-one patients with no pelvic relaxation, in whom total abdominal hysterectomies were performed for benign reasons, were used as the study and control groups, respectively. From each hysterectomy material, samples for histological examination were taken from the vaginal fascia and from the cardinal, the uterosacral and the round ligaments (4 samples for each patient). The amount of collagen, cellularity and elastic fibers within the connective tissue were evaluated and scored by the co-author pathologist. Mann-Whitney U and Student t tests were used for the statistical analysis. The patients with pelvic relaxation had significantly higher scores of collagen and fewer scores of cellularity within the connective tissue samples, compared with the ones without relaxation (p < 0.01, p < 0.01). It was concluded that decreased fibroblasts and increased collagen content might be the key factors associated with pelvic support disorders.

Topics: Adult; Collagen; Connective Tissue; Elastin; Fascia; Female; Fibroblasts; Humans; Ligaments; Middle Aged; Reference Values; Uterine Prolapse; Uterus; Vagina

Abnormal connective tissues may be a key factor in the development of pelvic supportive disorders. Elastin gene transcripts and elastin synthesis in cultured fibroblasts derived from cardinal ligaments of patients with prolapsus uteri and compared them with those in fibroblasts from age-matched control patients were examined. Elastin mRNA steady-state levels and elastin synthesis were significantly down-regulated in quiescent fibroblasts from prolapsus uteri patients compared with quiescent control fibroblasts. Although transforming growth factor beta 1 (TGF-beta 1) promoted elastin mRNA and protein levels in fibroblasts from both prolapsus uteri and control patients, the maximum levels of elastin gene transcripts and elastin synthesis in response to exogenous TGF-beta 1 were significantly lower in prolapsus uteri fibroblasts than control fibroblasts. These results suggest that the marked reduction in elastin gene transcripts and elastin production in fibroblasts cultured from elderly women with prolapsus uteri could lead to a paucity of ligament elastic fibres and thus may contribute to the loss of supportive function in uterine connective tissues.

Topics: Cells, Cultured; Elastin; Female; Fibroblasts; Gene Expression Regulation; Humans; Ligaments; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic; Uterine Prolapse