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. 2022 Mar 21;23(6):3401.
doi: 10.3390/ijms23063401.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

Wilke M Post  1 , Joanna Widomska  2 , Hilde Grens  1 , Marieke J H Coenen  3 , Frank M J Martens  4 , Dick A W Janssen  4 , Joanna IntHout  5 , Geert Poelmans  2 , Egbert Oosterwijk  4 , Kirsten B Kluivers  1
Affiliations

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

Wilke M Post et al. Int J Mol Sci. .

Abstract

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

Keywords: associated genes; associated proteins; gene expression; genetic variants; molecular background; protein expression; stress urinary incontinence.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Prisma flow chart [21]. Systematic selection of articles and main reasons for exclusion based on the Prisma 2020 statement. Abbreviations: SUI stress urinary incontinence, ROB risk of bias.
Figure 2
Figure 2
Quality assessment of human studies using the ROBINS-I tool. Abbreviations: BMI body mass index.
Figure 3
Figure 3
Quality assessment of animal studies using the SYRCLE tool.
Figure 4
Figure 4
Forest plot of collagen-related protein expression in human studies. This forest plot shows the collagen-related protein expression differences between patients with SUI and controls, subdivided per menopausal status group. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
Figure 5
Figure 5
Forest plot of other extracellular matrix related protein expression and biomarker levels in human studies. This forest plot shows other extracellular matrix-related protein expression and biomarker level differences between patients with SUI and controls, subdivided per extracellular matrix metabolism-related theme. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
Figure 6
Figure 6
Forest plot of estrogen receptor-related protein expression in human studies. This forest plot shows estrogen receptor-related protein expression differences between patients with SUI and controls, subdivided per menopausal status group. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
Figure 7
Figure 7
Forest plot of hormonal biomarkers in the serum of premenopausal women. This forest plot shows differences in hormonal biomarkers in the serum between premenopausal patients with SUI and controls, subdivided per hormone. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
Figure 8
Figure 8
Forest plot of hormonal biomarkers in the serum of postmenopausal women. This forest plot shows differences in hormonal biomarkers in the serum between postmenopausal patients with SUI and controls, subdivided per hormone. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
Figure 9
Figure 9
Forest plot of neuron-specific marker-related protein expression in human studies. This forest plot shows differences in the protein expression of neuron-specific markers between patients with SUI and controls, subdivided per menopausal status group. Abbreviations: CI confidence interval, N number, SD standard deviation, SMD standardized mean difference, SUI stress urinary incontinence.
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