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Prospective cohort of biochemical, protein and immunohistochemical markers of muscle fiber and extracellular matrix of the rectus abdominis muscle of Hyperglycemia and gestational-specific urinary incontinence as predictor of UI 6-12 months post-cesarean

Grant number: 18/02979-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): September 01, 2018
Effective date (End): August 31, 2022
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Iracema de Mattos Paranhos Calderon
Grantee:Raghavendra Hallur Lakshmana Shetty
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:16/01743-5 - The new gestational triad: hyperglycemia, urinary incontinence (UI) and biomolecular profile as a long-term predictor for UI: a prospective cohort study: translational research with biodevice with stem cells for muscle regeneration in diabetic rats, AP.TEM


The research group "Diabetes and pregnancy - clinical and experimental", in the Botucatu Medical School, has investigated since 2006, the pathophysiology of gestational diabetes (GDM) and Mild Gestational Hyperglycemia (MGH) and their relationships with Pelvic Floor Muscle Dysfunction (PFMD) and Urinary Incontinence (UI) in clinical and experimental studies. After critical analysis with national and international partners, it was observed that there were some gaps that need to be filled with pre-clinical and clinical complex studies. Objectives: to analyze the influence of the association between gestational hyperglycemia (HG) considering GDM and MGH, "Pregnancy-Specific UI (PSUI)" and profile (morphological, functional, biochemical, molecular and OMICs) of Gestational Hyperglycemic Myopathy (GHM) in the Rectus Abdominis Muscles (RAM) and Pelvic Floor Muscles (PFM); analyze the triad, HG, "PSUI" and profile of the GHM, the incidence of UI 6-12 months postpartum and morphological, functional and biochemical profile, within the four cohorts formed by the combination of HG and "PSUI"; to evaluate the effect of a latex biodevice coated with mesenchymal stem cells in the regeneration of urethral muscle and RAM after cesarean section in pregnant rats with moderate Diabetes in morphological profile, microvascular, molecular and OMICs; and determine the scientific evidence through systematic review of the effectiveness of exercise on the PFMD and "PSUI" in pregnant women with HG. Materials and methods: in the clinical study, participants will be selected from January 2016 to December 2019 in the Perinatal Diabetes Research Center of UNESP, at the Maternal Hospital - FAMEMA and the Regional Hospital of Assis City. The total number of participants will be 160, considering the four cohorts that will be constituted. Biochemical analysis will be performed on blood samples obtained from the study participants, to ascertain the levels of CCL7, Relaxin, Ca, PTH, calcitonin, vitamin D, glucose and insulin. In terms of the PFMs, the following evaluations will be conducted: Functional Assessment of pelvic floor, electromyography (EMG) and ultrasound (US). In terms of the RAM, the following evaluations will be conducted: EMG and US, at the time of cesarean ex vivo contractility obtained by Myograph, and morphological profiles (ultrastructure of muscle fibers and extracellular matrix), molecular (gene and protein expression in muscle fibers and extracellular matrix) and OMICs (transcriptomics, proteomics and metabolomics). For the experimental study, pregnant Wistar rats divided into groups will be used (n=20 each), non-diabetic and diabetic, to undergo the installation of a biodevice of latex membrane coated mesenchymal stem cells implanted into the urethral striated muscle and RAM. The systematic review study will follow the accepted rules and be registered with the Cochrane Collaboration. For statistical analysis, associations will be considered statistically significant at p < 0.05. Analysis will be done with SPSS v21.0 software. Expected results: to characterize the GHM; that the proposed triad is a predictor of UI and PFMD after 6-12 months post-partum; to establish markers for diagnosis and future therapies; to highlight the first line of preventive or rehabilitative intervention for muscle dysfunction and "PSUI"; that "PSUI" in pregnant women with GH be included and considered apublic health problem as well as a clinical complication, and thus represent a new tool in defining the longterm maternal impact; and that the biodevice be considered for muscle regeneration in future clinical trials; and that this proposed translational approach will bring this research to the forefront of knowledge in women's health, once as yet unpublished analysis methodologies can be applied in areas that complement the problematic approach of medical/social interest. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALVES, FERNANDA CRISTINA BERGAMO; DE OLIVEIRA, RAFAEL GUILEN; REYES, DAVID RAFAEL ABREU; GARCIA, GABRIELA AZEVEDO; FLORIANO, JULIANA FERREIRA; SHETTY, RAGHAVENDRA HALLUR LAKSHMANA; MARECO, EDSON ASSUNCAO; DAL-PAI-SILVA, MAELI; PAYAO, SPENCER LUIZ MARQUES; SOUZA, FATIMA PEREIRA DE; et al. 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. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 21, p. 20-pg., . (18/10661-8, 19/05710-2, 16/01743-5, 17/21783-4, 18/26305-6, 18/02979-8)
RUDGE, MARILZA V. C.; ALVES, FERNANDA C. B.; HALLUR, RAGHAVENDRA L. S.; OLIVEIRA, RAFAEL G.; VEGA, SOFIA; REYES, DAVID R. A.; FLORIANO, JULIANA F.; PRUDENCIO, CAROLINE B.; GARCIA, GABRIELA A.; REIS, FABIANA V. D. S.; et al. Consequences of the exposome to gestational diabetes mellitus. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1867, n. 2, p. 14-pg., . (18/02979-8, 16/01743-5, 18/26305-6, 21/10665-6, 17/21783-4, 19/05710-2, 18/10661-8)
CATINELLI, BRUNA B.; ROSSIGNOLI, PATRICIA S.; FLORIANO, JULIANA F.; CARR, ALINE M.; DE OLIVEIRA, RAFAEL G.; DOS SANTOS, NILTON J.; UBEDA, LARA C. C.; SPADELLA, MARIA ANGELICA; HALLUR, RAGHAVENDRA L. S.; SOBREVIA, LUIS; et al. Reversal of diabetic-induced myopathy by swimming exercise in pregnant rats: a translational intervention study. SCIENTIFIC REPORTS, v. 12, n. 1, p. 12-pg., . (18/03361-8, 18/02979-8, 17/21783-4, 16/01743-5)

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