Mouse urothelial genes associated with voiding behavior changes after ovariectomy and bladder lipopolysaccharide exposure

Acevedo-Alvarez, Marian; Yeh, Judy; Alvarez-Lugo, Lery; Lu, Ming; Sukumar, Nitin; Hill, Warren G.; Chai, Toby C.

doi:10.1002/nau.23592

Cited by 13 publications

(4 citation statements)

References 33 publications

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“…The decrease in bladder weight has also been observed in previous ovariectomy rat and rabbit models, and the reasons may be related to muscle atrophy and collagen fiber substitution [21][22][23][24]. Although this study did not deeply investigate the bladder function, the susceptibility to OAB and UTI caused by the ovariectomy animal model has been widely confirmed [7,[25][26][27]. It is well-known that estrogen receptors are widely distributed in the bladder [28], and obviously, estrogen can to some extent regulate bladder function.…”

Section: Discussionmentioning

confidence: 62%

Exploratory Metabolomic Analysis for Characterizing the Metabolic Profile of the Urinary Bladder under Estrogen Deprivation

Zhang,

Yang,

Song

et al. 2023

Preprint

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Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from ovarian removal or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusions: This study, for the first time, depicted the metabolic profile of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by estrogen deprivation.

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Section: Discussionmentioning

confidence: 62%

Exploratory Metabolomic Analysis for Characterizing the Metabolic Profile of the Urinary Bladder under Estrogen Deprivation

Zhang,

Yang,

Song

et al. 2023

Preprint

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“…The VSA has been used to accurately predict increased frequency with chemical cystitis and with age (44). It has been used to identify the impact of sex hormones on voiding function (1,35). It has been used to identify a diet-induced physiological change in voiding behaviors (confirmed by cystometry) (26,48).…”

Section: Technical Aspects For Performing Vsamentioning

confidence: 99%

Void spot assay: recommendations on the use of a simple micturition assay for mice

Hill

Zeidel

Bjorling

et al. 2018

American Journal of Physiology-Renal Physiology

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Investigators have for decades used mouse voiding patterns as endpoints for studying behavioral biology. It is only recently that mouse voiding patterns were adopted for study of lower urinary tract physiology. The spontaneous void spot assay (VSA), a popular micturition assessment tool, involves placing a mouse in an enclosure lined by filter paper and quantifying the resulting urine spot pattern. The VSA has advantages of being inexpensive and non-invasive, but some investigators challenge its ability to distinguish lower urinary tract function from behavioral voiding. A consensus group of investigators who regularly use the VSA was established by the National Institutes of Health in 2015 to address the strengths and weaknesses of the assay, determine whether it can be standardized across labs, and whether it can be used as a surrogate for evaluating urinary function. Here we leverage experience from the consensus group to review the history of the VSA and its uses, summarize experiments to optimize assay design for urinary physiology assessment, and make best practice recommendations for performing the assay and analyzing its results.

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“…Urine profiles of pterin compounds have the potential to become predictive biomarkers of bladder cancer (10). Moreover, Acevedo-Alavarez and colleagues (11) reported that mouse urothelial transcripts of Gch1 might play an important role in modulating voiding behavior changes.…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

Hozyasz

Mostowska²,

Kowal

et al. 2020

Iran J Pediatr

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Background: Hypospadias (HS) is one of the most common congenital malformations. Complications of corrective surgery in HS correlate with patients’ opinions on their voiding ability and sexual life as adults. Etiology of HS involves both genetic and environmental factors. GCH1, which belongs to recently identified urothelial genes influencing voiding behavior, encodes rate-limiting enzyme catalyzing the production of tetrahydrobiopterin (BH4). A requirement for BH4, a metabolite structurally related to folic acid and riboflavin, in embryonic development was reported. Objectives: The aim of the present study was to investigate the association of selected polymorphic variants of BH4 pathway genes with hypospadias. Methods: We performed an analysis of 6 SNPs of GCH1, PAH and AGMO-DGKB loci in a group of 166 boys with isolated hypospadias and a properly matched control group. Results: There was no evidence for either allelic or genotypic association with the risk of HS for the tested nucleotide variants (rs12425434, rs7485331, rs17128050, rs8004018, rs17128077, rs2191349). The lack of association with single SNPs was confirmed at the haplotype level. The exhaustive multifactor dimensionality reduction (MDR) analysis revealed no significant interactive effect of polymorphic variants of BH4 pathway genes on HS susceptibility. Conclusions: The presented results did not support an association between SNPs of GCH1 and PAH and the risk of HS.

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Mouse urothelial genes associated with voiding behavior changes after ovariectomy and bladder lipopolysaccharide exposure

Abstract: OVX mice persisted with increased voiding frequency after LPS. Urothelial genes that could mediate this voiding behavior include IL6, COX-2, and S-adenosylmethionine decarboxylase.

Cited by 13 publications

References 33 publications

Exploratory Metabolomic Analysis for Characterizing the Metabolic Profile of the Urinary Bladder under Estrogen Deprivation

Exploratory Metabolomic Analysis for Characterizing the Metabolic Profile of the Urinary Bladder under Estrogen Deprivation

Void spot assay: recommendations on the use of a simple micturition assay for mice

Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

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