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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 29  |  Issue : 2  |  Page : 73-80

Surgical menopause exacerbated high-fat and high-sugar diet-induced overactive bladder in a rat model


1 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital; Department of Urology, Kaohsiung Medical University Hospital; Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3 Translational Research Center, Cancer Center, Department of Medical Research, Kaohsiung Medical University, Kaohsiung, Taiwan
4 Graduate Institute of Medical Science, Kaohsiung Medical University, Kaohsiung; Department of Urology, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan
5 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
6 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital; Department of Urology, Kaohsiung Medical University Hospital; Department of Urology, College of Medicine, Kaohsiung Medical University; Graduate Institute of Medical Science, Kaohsiung Medical University; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

Date of Web Publication30-Apr-2018

Correspondence Address:
Yung-Shun Juan
Department of Urology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road Sanmin District, Kaohsiung 807
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_8_17

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  Abstract 

Objective: The pathophysiology mechanism of menopause in the metabolic syndrome-associated bladder dysfunction is still not clear. The major aims of the present study were to examine the impact of high-fat-high-sugar diet and surgical menopause-induced metabolic syndrome in overactive bladder (OAB). Methods: Female Sprague Dawley rats were feed with high-fat-high-sugar diet with/without ovariectomy surgery to mimic menopause and to induce metabolic syndrome. At 6 months after high-fat-high-sugar feeding, cystometrogram, physical indicator, and urine and serum biochemistry parameters were measured. Masson's trichrome stain and Western blots were carried out to examine the expressions of interstitial fibrosis, fibrosis-associated proteins, and muscarinic or purinergic receptors. Results: Bladder hyperactivity was induced accompanied by bladder interstitial fibrosis after 6 months of high-fat-high-sugar feeding, while surgical menopause exacerbated these bladder damages and enhanced interstitial fibrosis level. In addition, surgical menopause enhanced bladder dysfunction via overexpression of muscarinic and purinergic receptors. Conclusions: High-fat-high-sugar feeding induced bladder overactivity, while ovary hormone deficiency enhanced bladder interstitial fibrosis, exacerbated OAB syndrome, and increased muscarinic and purinergic receptors expressions.

Keywords: High-fat-high-sugar diet, metabolic syndrome, ovariectomy, overactive bladder


How to cite this article:
Tsao YH, Lee YC, Chuang SM, Lee YL, Shen JT, Geng JH, Wang HS, Jang MY, Yang KF, Juan YS, Wu WJ. Surgical menopause exacerbated high-fat and high-sugar diet-induced overactive bladder in a rat model. Urol Sci 2018;29:73-80

How to cite this URL:
Tsao YH, Lee YC, Chuang SM, Lee YL, Shen JT, Geng JH, Wang HS, Jang MY, Yang KF, Juan YS, Wu WJ. Surgical menopause exacerbated high-fat and high-sugar diet-induced overactive bladder in a rat model. Urol Sci [serial online] 2018 [cited 2018 May 24];29:73-80. Available from: http://www.e-urol-sci.com/text.asp?2018/29/2/73/228290


  Introduction Top


Almost 20%–30% of the middle-aged population is affected by metabolic syndrome. Such incidence varies from 8% to 24% in male [1] and from 7% to 46% in female.[2] People with metabolic syndrome have up to fivefold higher risk of type 2 diabetes and twofold to threefold higher risk of atherosclerotic cardiovascular disease than those without it. Metabolic syndrome was reported to contribute to overactive bladder (OAB) in humans and animal models. Studies on the relationship between metabolic syndrome and OAB revealed that men classified as having metabolic syndrome had increased odds of lower urinary tract symptoms (LUTSs).[3],[4] Dietary factors are of importance in the induction of metabolic syndrome.[5] In animal models, feeding rats with hypercholesterol diet induced bladder detrusor cell hypertrophy, decreased bladder capacity, and produced the symptoms/signs of OAB.[6] Using fructose-fed rat model, unstable bladder contractions were found to occur in 62.5% of male rats compared with the control. These findings supported the role of metabolic disturbance in the etiology of LUTSs.[7],[8] Animal studies also revealed that feeding rats with high fat high sugar (HFHS) or fructose-rich diet induced the characteristics of metabolic syndrome.[5],[6],[7],[8],[9],[10] In those fructose-fed rats with detrusor overactivity, there were dysregulation of smoothelin and decreased expression of Bcl-2 with a subsequent increase in apoptotic cells in the bladder wall. Moreover increases in the mRNA and protein expressions of M2 and M3 – muscarinic receptors – and P2X1 – purinergic receptors – were associated with functional evidence of detrusor overactivity fructose-fed rats.[6],[11]

Previous studies reported that in postmenopausal women, there was an increasing incidence of metabolic syndrome.[12],[13] Postmenopausal women, as a result of ovary hormone deficiency and age-related changes, were subjected to a number of urological dysfunctions, including OAB, stress urinary incontinence, and recurrent urinary tract infections.[14],[15] Changes in voiding patterns occurred in ovariectomized rats, which could be attributed to ovary hormone deficiency. Estrogen replacement decreased the frequency of voiding but did not return the animals to the preovariectomized pattern.[16] Estrogen deficiency also caused atrophy of bladder smooth muscle (SM), decreased SM contractility, enhanced mucosal atrophy, diminished bladder blood flow, and eventually resulted in tissue hypoxia.[17],[18]

Our previous investigation showed that ovariectomy (OVX) increased oxidative damage, enhanced voiding frequency, and decreased bladder compliance.[19] Understanding the pathophysiology of metabolic perturbation with/without menopause in the bladder might provide potential factors underlying metabolic syndrome-associated overactive bladder. In extension of our previous investigations of OAB and bladder dysfunction,[19],[20] the present work investigated HFHS-induced metabolic syndrome with/without surgical menopause in rat model. The obtained information attempted to provide valuable insights into potential factors that might play crucial role in metabolic syndrome and bladder overactivity.


  Methods Top


Animals and feeding protocol

The experimental procedures were approved by the Committee for the Use of Experimental Animal of Kaohsiung Medical University and were adhered to the guidelines of the National Institute of Health for the use of the experimental animals. Female Sprague Dawley rats initially weighing 200–250 g were divided into three different groups: (a) normal rat chow diet (the control) group, (b) the high-fat and high-sugar diet-treated (the HFHS-treated) group, (c) bilateral OVX combined with HFHS diet group (the OVX-HFHS-treated) group. The major ingredients of high-fat and high-sugar (HFHS) diet (DyEts Inc, USA; DyEt, # 102829) included casein (200 g/kg; 716 kcal/kg), soybean oil (25 g/kg; 225 kcal/kg), and fructose (575 g/kg; 2300 kcal/kg). The fat content of the HFHS diet was predominantly saturated. In OVX, both ovaries were excised through bilateral abdominal incisions under halothane anesthesia, and every effort was made to minimize suffering and the number of animals used throughout the experiment. After bilateral OVX, the rats were allowed to recovery for 2 weeks and then received HFHS diet feeding during the following 6-month period.[20]

Estradiol concentration by enzyme-linked immunosorbent assay

A quantity of 1 mL of blood was obtained at the termination of the experiment for estradiol analyses. Blood was separated by centrifugation at 4°C. The microtiter wells of the 17-β estradiol enzyme-linked immunosorbent assay (ELISA) kit (Cayman Chemical Co., Ann Arbor, MI, USA) were coated with an antibody directed toward a unique antigenic site on the estradiol molecule. After addition of the substrate solution, the intensity of color developed was inversely proportional to the concentration of estradiol in the rat sample as measured by ELISA (BioTek ELx800, BioTek, Bad Friedrichshall, Germany).[20] The mean absorbance values for each set of standards and serum samples of experimental rats were calculated. A standard curve was obtained by plotting the mean absorbance obtained from each standard against its concentration with value.[20]

Evaluation of metabolic parameters

Blood samples were collected for biochemical analysis. Serum activity of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and the concentrations of triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, glucose, and insulin were determined using an automated analyzer (Selectra Junior Spinlab 100, Vital Scientific, Dieren, Netherlands; Spinreact, Girona, Spain) according to the manufacturers' instructions. To evaluate proteinuria status, 24-h urine sample was collected as a precise indicator according to the National Kidney Foundation.[21] Total protein in the urine was measured by colorimetric assay, using pyrogallol red as dye-binding (Wako Diagnostics and Chemicals USA Inc.). During the experimental periods, physical indicators, including body weight, bladder weight, waist circumference, systolic pressure, diastolic pressure, and mean arterial pressure (MAP, calculated as 1/3 systolic pressure +2/3 diastolic pressure) were measured monthly.

Metabolic cage study and cystometrogram studies for micturition pattern

After 6 months of treatment, rats were placed in individual metabolic cages (R-2100; Lab Products, Rockville, Maryland). The 24-h micturition frequency and voided volume were determined using a cup especially fitted to a transducer (MLT 0380, ADInstruments, Colorado Springs, CO, USA). In the same time, the volume of water intake and urine output were collected and were measured.

The isovolumetric cystometrograms (CMGs) were performed as previously described.[22] In brief, for each experiment, rats were anesthetized with zoletil 50 (1 mg/kg IP). The bladder catheter (PE50 tube) was connected to both a syringe pump (KD Scientific 100, KD Scientific, Holliston, MA, USA) and a pressure transducer (MLT 0380, ADInstruments, Colorado Springs, CO, USA). This urethral catheter was used to fill the bladder and to measure bladder pressure. Before beginning of each CMG, the bladder was emptied and saline was then infused at a steady rate (0.08 ml/min), during which pressure was measured via a small-volume pressure transducer in line with the catheter. A voiding contraction was defined as an increase in bladder pressure that resulted in urine loss. The CMG was recorded until the bladder pressure was stable and at least five filling/voiding cycles were measured in each rat. Pressure and force signals were amplified (ML866 PowerLab, ADInstruments), recorded on a chart recorder, and digitized for computer data collection (LabChart 7, ADInstruments, Windows 7 operating system). CMG variables recorded for each animal included filling pressure (pressure at the beginning of the bladder filling), micturition pressure (the maximal bladder pressure during micturition), micturition interval (time between micturition events), voiding volume, and presence or absence of nonvoiding contractions.

Histological study by Masson's trichrome stain

After cystometric studies, experimental rats were perfused with saline solution through the left ventricle, and the bladders were removed and cut open in a sagittal direction. The bladder tissue samples in the same area from different groups were embedded in paraffin blocks, and serial sections of 5 μm thickness were obtained. Deparaffinized sections were stained with Masson's trichrome stain (Masson's trichrome stain kit, DAKO, Glostrup, Denmark). The standard Masson's trichrome staining procedure was followed to stain connective tissue in blue and detrusor smooth muscle (DSM) in red.[19],[20] The transverse section of each specimen was captured by a digital camera in ten random, nonoverlapping frames at ×400 magnification, and the entire bladder wall thickness was included in each region analyzed. The color setting and image-associated quantification were determined using image analysis software (Image-Pro Plus, Media Cybernetics, MD, USA). The blue-stained collagen and red-counterstained DSM were highlighted for each image.

Protein isolation and Western blot analysis

According to the previously described method,[19] frozen tissue samples of the bladder were homogenized on ice in the buffer (50 mM Tris, pH 7.5, 5% Triton-X100) containing the halt protease inhibitor cocktail (Pierce, Rockford, IL, USA) at 100 mg/mL. An amount of 30 μg of protein from the bladders was loaded on sodium dodecyl sulfate polyacrylamide electrophoresis gels and transferred to polyvinylidene fluoride membranes (Immobilon-P, Millipore, MA, USA). Immobilon-P membranes were incubated with primary antibodies to the following markers, receptors, proteins, and enzyme complexes. These include CHRM2 (M2; Epitomics, mouse monoclonal IgG1, 1:1000; MW ~52 kDa), CHRM3 (M3; Alomone Labs, rabbit polyclonal IgG, 1:1000; MW ~66 kDa), P2X3 (Novus, rabbit polyclonal IgG, 1:1000; MW ~61 kDa), vesicular acetylcholine transporter (VAChT; Acris, mouse monoclonal IgG1, 1:1000; MW ~55 kDa), transforming growth factor beta (TGF-β, R&D, rabbit polyclonal IgG 1:1000; MW ~15 kDa), fibronectin (BD, 1:1000, mouse monoclonal IgG1; MW ~15 kDa), type 1 collagen (Abcam, 1:1000, rabbit polyclonal IgG; MW ~15 kDa), and β-actin (Millipore, mouse monoclonal IgG2b, 1:1000; MW ~43 kDa). In each experiment, negative controls were performed without the primary antibody.

Statistical analysis

Analysis of variance, followed by the Bonferroni test and two-way analysis of variance for individual comparison, was conducted for the above experiments. The mean, standard deviation (SD), and P values were calculated on triplicate experiments. Student's t-test was used to calculate P values for comparison. The significant level was set at a P < 0.05.


  Results Top


Effects of surgical menopause and HFHS diet on physical characteristics and biochemical parameters in different experimental groups

There was no noticeable difference in estradiol level by ELISA assay between different groups before bilateral OVX [Table 1]. However, 2 weeks after OVX, the serum estradiol concentration was 42.8 ± 6.2 pg/ml for the control group, 37.7 ± 5.5 pg/ml for the HFHS diet-treated group, and 17.6 ± 4.1 pg/ml for the OVX-HFHS-treated group. As expected, surgical menopause meaningfully decreased serum estradiol concentrations.
Table 1: General characteristics and biochemistry parameters of serum and urine for different experimental groups

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General physical characteristics, including body weight, waist circumference, systolic pressure, and MAP are also shown in [Table 1]. After feeding with HFHS diet for 6 months, the characteristics of metabolic syndrome developed in the HFHS-treated and OVX-HFHS-treated groups, as evidenced by significant increases in body weight, waist circumference, systolic pressure, and MAP as compared to the control group. Especially, the OVX-HFHS-treated group showed a meaningful increase in body weight, waist circumference, and systolic pressure compared to the control group, which presented typical metabolic syndrome, including obesity (body weight and waist circumference), and minor hypertension (systolic pressure and MAP).

There was no significant difference in water intake or urine output analysis between the different groups. However, the HFHS-treated and OVX-HFHS-treated groups showed significant increases in bladder weight, urine glucose, urine protein, and the ratio of urine protein to creatinine as compared to the control group. Specifically, rats in the OVX-HFHS-treated group exhibited higher body weight, bladder weight, urine protein, and glucose than those in the HFHS-treated group [Table 1].

The serum parameters associated with metabolic syndrome, including triglycerides, cholesterol, LDL, and glucose, were significantly elevated in the HFHS-treated and OVX-HFHS-treated groups compared to the control group. However, there was no meaningful difference in the insulin level between the different groups. Meanwhile, these metabolic syndrome-associated parameters were even higher in the OVX-HFHS-treated group compared to the HFHS-treated group.

Bladder function and voiding behavior

[Table 1] and [Figure 1] report the urodynamic parameters and representative tracings of metabolic cages study, including micturition frequency, micturition pressure, voided volume, and nonvoided contraction between micturition. There were increase in micturition frequency (1.8-fold) and peak micturition pressure (1.3-fold) but decrease in micturition interval and bladder volume (0.6-fold) in the HFHS-treated group as compared with those in the control group [Table 1]. Moreover, the OVX-HFHS-treated group exhibited noticeable increases in micturition frequency (3.0-fold), peak micturition pressure (1.6-fold), and nonvoiding contraction (stars) but decreases in micturition interval and bladder volume (0.3-fold), as compared with the control group [Figure 1] and [Table 1]. Especially, OVX-HFHS-treated group enhanced micturition frequency (1.7-fold), peak micturition pressure (1.3-fold), and nonvoiding contraction (stars) but reduced voiding volume (0.5-fold), as compared with the HFHS-treated group. These results demonstrated that the OVX-HFHS-treated rats caused significant bladder hyperactivity and abnormal detrusor activity with an increase in micturition frequency.
Figure 1: The effects of surgical menopause on bladder cystometric parameters and voiding behavior in HFHS feeding induced metabolic syndrome. (a) Cystometry recordings illustrating maturation pressure and voiding frequency including voiding contractions (arrows) and nonvoiding contractions (stars). (b) Tracing analysis of 24-h voiding behavior by metabolic cage. The recordings showed that the ovariectomy-HFHS-treated group significantly increased bladder intravesical pressure, voiding contractions, nonvoiding contractions, and micturition frequency than the other groups

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Effects of surgical menopause and epigallocatechin gallate on bladder muscarinic and purinergic receptors

[Figure 2] shows representative Western blots for the protein expressions of CHRM2 (M2), CHRM3 (M3) muscarinic and P2X3 purinergic receptors, as well as statistical comparisons in the bladder of different groups. In comparison with the control, the protein expressions of muscarinic and purinergic receptors were increased by two-fold for P2X3 receptor in the HFHS-treated rats and by threefold for M2, M3, and P2X3 receptors in the OVX-HFHS-treated rats. Furthermore, the protein expression of VAChT was increased by twofold in the OVX-HFHS-treated group as compared with the control and HFHS groups. These results demonstrated that the OVX-HFHS-treated rats exhibited bladder hyperactivity with increases in muscarinic and purinergic receptors and VAChT as compared with those in the control and HFHS-treated groups.
Figure 2: The effects of surgical menopause on bladder muscarinic and purinergic receptors in HFHS feeding induced metabolic syndrome. Representative Western blots of the muscarinic and purinergic receptors (a) and analysis of optical density for M2, M3, and P2X3 receptors (b) and vesicular acetylcholine transporter (c). Values were the mean ± standard deviation for n = 8. *P < 0.05; **P < 0.01 versus the control group. #P < 0.05; ##P < 0.01 versus the other group

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The bladder histological features of surgical menopause in HFHS feeding-induced metabolic syndrome

Masson's trichrome stain was performed to investigate the pathological changes of the bladder after HFHS with/without OVX treatment [Figure 3]. In the control group [Figure 3]A and [Figure 3]3A'], there were 3–5 layers of urothelial layer and only sparse collagen distributing in suburothelial layer. Similarly, there was only sparse collagen accumulation between DSM bundles in the muscular layer. On the contrary, there was significant interstitial fibrosis and collagen accumulation (arrows) between DSM bundles in the HFHS-treated and OVX-HFHS-treated bladders [Figure 3]A,[Figure 3]B,[Figure 3]C. The OVX-HFHS-treated group also showed thinning of urothelial mucosa (black arrowhead) [Figure 3]C.
Figure 3: The pathological features of surgical menopause in HFHS feeding induced metabolic syndrome. Representative photomicrographs showed Masson's trichrome staining of the control group (A), HFHS group (B), and HFHS-ovariectomy group (C). Masson's trichrome stain showed that the blue-stained collagen and the red-counterstained detrusor smooth muscle were highlighted for each image. In the control group (A and A'). There were significant interstitial fibrosis and collagen accumulation (arrows) between detrusor smooth muscle bundles in HFHS (B and B') and ovariectomy-HFHS (C and C') treated bladders. The ovariectomy-HFHS-treated group revealed the increased bladder fibrosis (arrows), thinning urothelial mucosa (arrowheads)

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Moreover, the expressions of inflammatory and fibrosis markers (TGF-β, fibronectin, and type I collagen) at protein level were examined by Western blotting [Figure 4]. In comparison with the control bladders, the expression of TGF-β protein was significantly increased by 169.6% ± 18.5% in the HFHS-treated rats while by 323.8% ± 30.2% in the OVX-HFHS-treated rats. Moreover, the expression of fibronectin and collagen I was significantly increased in the HFHS-treated and OVX-HFHS-treated rats. These findings revealed that inflammatory and fibrosis markers expressions were significantly increased in the HFHS and OVX-HFHS, indicating an increase in bladder interstitial fibrosis.
Figure 4: The effects of surgical menopause on fibrosis markers of the bladders in the HFHS feeding-induced metabolic syndrome. (a) Representative Western blots for fibrosis marker expression (b) and analysis of optical density for transforming growth factor beta, fibronectin, and type I collagen in each group. Results were normalized as the control = 100%. Values were the mean ± standard deviation for n = 8. *P < 0.05; **P < 0.01 versus the control group. ##P < 0.01 versus the other group

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  Discussion Top


The present study showed that surgical menopause and HFHS feeding induced OAB symptoms, such as increasing micturition frequency and peak micturition pressure, while diminishing bladder voided volume, resulted in bladder damage and interstitial fibrosis. These results demonstrated that ovarian hormone deficiency exacerbated HFHS-induced bladder overactivity and interstitial fibrosis.

Metabolic syndrome and diabetes are known risk factors for the development of LUTS.[8],[23] It is unclear whether reducing insulin resistance and central obesity-related chronic inflammation and oxidative stress could prevent the onset of OAB or improve the outcome of treatment.[24] Previous investigations reported that clinically, there were linear associations between LUTS and increased abdominal fat mass, plasma glucose, and LDL cholesterol.[25] Moreover, in diabetic patients, multiple organs including heart and liver showed impaired mitochondrial function, decreased ATP generation and oxidative capacity, increased reactive oxygen species production and abnormal morphology, and decreased mitochondrial calcium uptake.[26]

Women with a higher degree of abdominal obesity are especially susceptible to type 2 diabetes, and women with diabetes have a higher relative risk of chronic heart disease than men with diabetes.[27] Postmenopausal women as a result of ovary hormone deficiency and age-related changes are subject to a number of urological dysfunctions, including OAB symptoms, stress incontinence, and recurrent urinary tract infection.[14] In ovariectomized rabbits treated with estrogen, their bladders were found to have greater bladder compliance and lower collagen to SM ratios than those in ovariectomized animals.[28] Our previous study suggested that ovary hormone deficiency could lead to OAB symptoms. OVX significantly increased the bladder fibrosis, enhanced bladder fibrosis markers, expanded bladder apoptotic cells, and augmented oxidative stress damage.[19],[20]

In the present study, feeding rats with HFHS diet for 6 months clearly induced metabolic syndrome, including fatty liver, swollen, and edematous appearance, and increased body weight, waist circumference, and systolic pressure. These HFHS-treated and OVX-HFHS-treated rats also increased micturition frequency and peak micturition pressure, enhanced the expression of P2X3 purinergic receptors, and raised oxidative stress and interstitial fibrosis. Particularly, OVX-HFHS-treated rats showed even more severe bladder hyperactivity with significant increases in M2 and M3 muscarinic and P2X3 purinergic receptors. Other previous study indicated that after 3 months feeding of fructose-enriched diet, rats showed insulin resistance, hyperlipidemia, and hypertension, resulting in detrusor overactivity and remarkable morphological changes of the bladder. Moreover, 6-month fructose feeding significantly decreased bladder contractility, upregulated M2 and M3 – muscarinic – as well as P2X1 – purinergic – receptors, and reduced nerve density and mitochondria degeneration contributed to OAB symptoms in rats with metabolic syndrome.[6],[11],[29] These findings indicated that chronic inflammation and myopathy induced by metabolic perturbations were the causes of bladder malfunction. These results supported the proposal that ovary hormone deficiency and HFHS diet induce OAB syndromes via muscarinic (M2 and M3) and purinergic (P2X3) receptors overexpression.

Our findings are supported by our previous study in which there were significant DSM atrophy and interstitial fibrosis in ovariectomized rats.[18] TGF-β expression was markedly increased under long-term HFHS feeding, while surgical menopause further exacerbated this pro-inflammatory protein expression. The augmented TGF-β expression and increased fibronectin and type I collagen expressions in estrogen-deprived bladders subjected to HFHS feeding showed ovary hormone may play a protective effect on metabolic syndrome induced bladder interstitial fibrosis. Bladder DSM and urothelial cells synthesize both type I and type III collagen, whereas type I collagen was present in the bladder extracellular matrix and exhibited greater deposition in the lamina propria. Increased accumulation and distribution of collagen and fibronectin might correspond to altered bladder compliance in the present study. Besides the increase in fibronectin and type I collagen expressions, Masson's trichrome stain demonstrated that HFHS feeding with or without surgical menopause increased the collagen-to-DSM ratio. These results demonstrated that estrogen exhibited strong antifibrotic effects when the bladder was subjected to metabolic syndrome-induced damage.

There are several limitations of the present study:First, an OVX combined with normal diet group was not included in the present study to evaluate the pure effect of surgical menopause. Second, we did not measure the postvoid residual urine volume; therefore, we cannot evaluate the voiding efficiency of each animal.


  Conclusions Top


HFHS feeding enhanced bladder overactivity, increased muscarinic and purinergic receptors expressions, and exacerbated bladder interstitial fibrosis; while ovary hormone deficiency further exacerbated bladder interstitial fibrosis, intensified OAB syndrome, and increased muscarinic and purinergic receptor expressions.

Acknowledgments

Research reported in this publication was supported by the Ministry of Health and Welfare, Executive Yuan (MOHW103-TD-B-111-05), in part by the Department of Medical Research, Kaohsiung Medical University Hospital grant (KMUH 102-2R41, KMUH103-3R42, KMUH 104-4R45), and Kaohsiung Municipal Hsiao-Kang Hospital grant (Kmhk-102-022, Kmhk-102-023, Kmhk-103-021, Kmhk-104-021).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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