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Prospective cohort of the omic biomarkers of the abdominal rectus muscle of pregnant women with hyperglycemia and pregnancy-specific urinary incontinence as predictors of urinary incontinence 6-12 months postpartum.

Grant number: 19/05710-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): May 01, 2019
Effective date (End): March 31, 2023
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Marilza Vieira Cunha Rudge
Grantee:Fernanda Cristina Bérgamo Alves
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


Introduction: The research group "Diabetes and Pregnancy - Clinical and Experimental" at Botucatu-Unesp School of Medicine has been investigating since 2006 the pathophysiology of gestational diabetes and mild gestational hyperglycemia (GHL) and its relationships with dysfunctions pelvic floor muscle (DMAP) and urinary incontinence (UI) in clinical and experimental studies. After critical analysis in the group and with national and international partners of the results obtained, there were large gaps that need to be filled with more complex preclinical and clinical studies. Objectives: To analyze the influence of the association between gestational hyperglycemia (HGG) considering GDM and HGL, "IUEG" and the morphological, functional, biochemical, molecular and erotic profile of "gestational hyperglycemic myopathy" MHG ") of the rectus abdominis muscle (ARM) and pelvic floor muscles (MAPs); , the incidence of UI 6-12 months postpartum (PP) and morphological, functional and biochemical profile, within the four cohorts constituted by the combination of HGG and "IUEG" ; to evaluate the effect of rubber latex biodevic with mesenchymal stem cells on regeneration of urethral muscle and ARM after cesarean section in pregnant rats with moderate diabetes in the morphological, microvascular, molecular and theomic profile; and to determine the scientific evidence, through a systematic review, of the effectiveness of the exercises on DMAP and "UGIR" in pregnant women with HG. Materials and Methods: In the clinical study, participants will be selected between January 2016 and December 2019 at the FMB UNESP Perinatal Diabetes Research Center, at the Risk Pregnancy Clinic of the FAMEMA Maternal and Child Hospital and at the Regional Hospital of Assis. The total number of participants will be 160 considering the four cohorts that will be constituted. An analysis of the biochemical profile obtained by the blood tests of the levels of CCL7, Relaxin, Ca, PTH, calcitonin, vitamin D, glucose and insulin will be performed; (EMG) and Ultrasonography (US), EMG and US, at the time of cesarean section, will be performed the ex vivo contractility obtained by the Miographer, and the morphological profiles ( ultrastructure of muscle fibers and extracellular matrix), molecular (Genetic and Protein Expression of muscle fibers and the extracellular matrix), and ómico (transcriptomic, proteomic and metabolomic). For the experimental study, pregnant Wistar rats will be used, divided into nondiabetic and diabetic groups (n = 20 each), which will be submitted to the installation of latex biomembrane biodevic coated with mesenchymal stem cells, implanted in the urethral striated musculature and MRA . The Systematic Review study will follow the standards and will be recorded in the Cochrane Collaboration. In the statistical analysis with SPSS v21.0 software, the relationships will be considered statistically significant at p <0.05. Expected results: Characterize the "MHG"; that the proposed triad be a predictor of UI and DMAP 6-12 months PP; define markers for diagnosis and in future therapies; evidence the first line of preventive or rehabilitative intervention for muscular dysfunctions and "UGI"; that the "UGI" in HGG be considered and included as a public health problem and as clinical intercurrence, becoming a new tool in the definition of maternal long term impact; that biodevic is considered for regeneration of the musculature in future clinical studies; and that this proposed translational approach will bring this research to the frontier of knowledge in the area of Women's Health, since unpublished analysis methodologies are being applied in the area that complement each other in the problematic approach of medical / social interest.

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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)

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