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Influence of macrophage depletion in pubic symphysis remodeling of C57BL6 mice during late pregnancy and postpartum

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Author(s):
Bianca Gazieri Castelucci
Total Authors: 1
Document type: Master's Dissertation
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Aureo Tatsumi Yamada; Valdemar Antonio Paffaro Junior
Advisor: Paulo Pinto Joazeiro
Abstract

The pubic symphysis (PS) is part of the musculoskeletal system elements that provide support to the pelvic organs. In mice, this fibrocartinaginous joint undergoes hormonally regulated changes during pregnancy involving the pubic bones reabsortion and formation of an elastic ligament (IpL) that leading to a safe delivery. At this period, the uterine cervix (UC) also undergoes an extensive remodeling sharing some similarities with the IpL tissue like connective tissue composition, cell proliferation and hormonal regulation of that process. Although some findings relate the relaxation of PS and UC to the activation of a pro-inflammatory response without the granulocytes involvement, others leukocytes participation in PS remodeling at the delivery and postpartum were not well investigated in mice. In order to characterize aspects of the participation of leukocytes in the PS remodeling we conducted the morphological characterization and analysis of gene expression of these cells during relaxation (12, 18 and 19 days of pregnancy) and the remodeling of the PS postpartum (1 and 3dpp) associated with the depletion of monocytes / macrophages. Morphological analysis revealed the presence of positive cells for antigen 7/4 and F4 / 80, monocytes and macrophages respectively, dispersed in the matrix and inside gaps of the IpL between the 18dp and 3dpp in the control and treated groups. In control group, the real-time PCR analysis showed increased expression of the characteristic inflammatory monocytes receptor (Ccr2) at the interpúbicos tissues on late pregnancy and postpartum. During pubic bones separation, evidences indicated that macrophages preferentially tend to polarize in the anti-inflammatory phenotype M2 (Arg1). At the relaxation of IpL pro-inflammatory M1 (Il1a, Tnfa) and anti-inflammatory M2 (I110) phenotypes was increased; in the meantime, parallel to the remodeling of the extracellular matrix necessary to the interpúbica joint reorganization at postpartum (1dpp), there was an increase in the expression of genes characteristic of M1 phenotype and decreasing in the Arg1 relative expression. Subsequently, at the 3dpp, despite the maintenance in expression levels of Il1a and Tnfa there was an increased in M2 phenotype-related genes expression (Il10, Arg1 and Tgfb) potentially involved in the activation of tissue repair mechanisms necessary to pubic bones reapproximation. Depletion of monocytes / macrophages at separation and interpubic tissue relaxation, as well as 3dpp favored the M1 macrophage phenotype polarization (Il1a, Tnfa), leading to changes in the extracellular matrix compression. This study shows that mononuclear phagocytes are important cells in the physiological process of mice PS remodeling during pregnancy, labor and postpartum. These cells act through finely regulated mechanisms to ensure the successfull tissue repair of the pelvic support structures in mice (AU)

FAPESP's process: 12/25038-8 - Influence of Macrophage depletion in C57BL6 mouse Pubic Symphysis Remodeling during the late Pregnancy and Postpartum
Grantee:Bianca Gazieri Castelucci
Support type: Scholarships in Brazil - Master