4.7 Article

Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence

Journal

Publisher

MDPI
DOI: 10.3390/ijms232112864

Keywords

gestational diabetes mellitus (GDM); pregnancy-specific urinary incontinence (PSUI); rectus abdominis muscle (RAM); transcriptomic profile; gestational diabetic-induced myopathy (GDiM)

Funding

  1. Brazilian Public Health System (SUS)
  2. Sao Paulo Research Foundation (FAPESP) [2016/01743-5, 2019/05710-2, 2018/26305-6, 2018/10661-82017/21783-4, 2018/02979-8]
  3. CNPq-Conselho Nacional de Desenvolvimento Cientifco e Tecnologico [305116/2018-5]
  4. FAPESP
  5. Fondo Nacional de Desarrollo Cientifico y Tecno-logico (FONDECYT), Chile [1190316]
  6. International Sabbaticals (University Medical Centre Groningen, University of Groningen, The Netherlands) from the Vicerectorate of Academic Affairs, Academic Development Office of the Pontificia Universidad Catolica de Chile

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Gestational diabetes mellitus (GDM) is a window of opportunity for predicting future complications such as type 2 diabetes mellitus and pelvic floor muscle disorders. This study focuses on the transcriptome profiling of the rectus abdominis muscle (RAM) in GDM women and identifies differentially expressed genes associated with muscle structure, muscle protein synthesis, muscle damage repair, and glycogenesis. These findings shed light on the molecular mechanisms of GDM and may lead to innovative interventions for preventing and treating post-GDM urinary incontinence.
Gestational diabetes mellitus (GDM) is recognized as a window of opportunity for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

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