Skeletal muscle organoid of pregnant women with Gestational Hyperglycemia and pregnancy-specific Urinary Incontinence as funcional 3D model to research biomarkers of Gestational Hyperglycemic Myopathy

• Grant number: 18/26305-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2021
• End date: July 31, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Marilza Vieira Cunha Rudge
• Grantee: Rafael Guilen de Oliveira
• 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

Abstract

Clinical and experimental studies from the research group "Diabetes and Pregnancy - Clinical and Experimental" have shown that Hyperglycemia in Gestation (HGG) associated with Urinary Incontinence - Specific of Gestation (IU-EG) increases the risk of developing Urinary Incontinence (IU) and Pelvic Floor Muscular Dysfunction (DMAP) 2 years after cesarean delivery. Translational studies in pregnant rats with moderate and severe diabetes have evidenced the presence of "diabetic myopathy", but there are still a number of gaps to be filled. Animal models and classical cell cultures have allowed important advances in this issue, however, there is limited research potential with traditional cell cultures because they do not represent tissue in vivo; and with animal models and clinical experimentation for ethical reasons. Three-dimensional cultures, such as organoids, emerge as a promising alternative because they enable the co-culture of different cell types to structure in an analogue tissue, allowing the establishment of a parallel to human tissues in vivo. Objective: in this project we propose to construct the skeletal muscle organoid of pregnant women with HGG as a functional 3D model of human tissue and to test their feasibility and representativeness for the investigation of gestational diabetic myopathy biomarkers. Method: the organoid will be developed from rectal abdominal biopsy material collected at the cesarean, from pregnant women in 4 groups: normoglycemic continent, normoglycemic incontinent, hyperglycemic continent and hyperglycemic incontinent. Muscle cells will be isolated and maintained in 2D culture until tridimensionality induction. After the organoid development, morphofunctional tests will be applied to verify the viability of the organoid as a representative model of the human rectus abdominis muscle in gestational myopathy. Expected results: it is expected to develop the representative and viable organoid in the context of translational Medicine. (AU)

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)

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., 2023-02-01. (18/02979-8, 16/01743-5, 18/26305-6, 21/10665-6, 17/21783-4, 19/05710-2, 18/10661-8)

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., 2022-11-01. (18/10661-8, 19/05710-2, 16/01743-5, 17/21783-4, 18/26305-6, 18/02979-8)