Phenotypic modulation of fibroblastic cells in mice pubic symphysis during pregnancy, partum and postpartum

Abstract

In many species, the cartilaginous pubic symphysis of the pregnant female is gradually replaced by a fibrous connective tissue, forming a flexible and elastic interpubic ligament. This newly formed ligament is responsible for the separation of the pubic bones, enabling safe delivery of the young. Following labor, the ligament undergoes rapid involution. To our knowledge, no previous work has focused on the phenotypic modulation that is responsible for the changes present at the interpubic ligament throughout the relaxation and closing of the symphysis. The purpose of this study was to investigate the ultrastructural features and immunophenotype of the peculiar cell type found in the pubic symphysis of cycling, pregnant and postpartum mice. In particular, immunohistochemistry studies were conducted on the expressions of the cytoskeletal proteins desmin, vimentin and alpha-smooth muscle actin (alpha-SMA). During pregnancy, the pubic symphysis cells always expressed alpha-SMA, whereas the expression of vimentin and desmin was transient from early pregnancy to postpartum. Furthermore, the expression patterns of these three cytoskeletal proteins were distinct. Cells present in the medial region of the mouse symphysis in cycling and at D12 displayed ultrastructural features characteristic of a typical fibroblast. In contrast, during the last week of pregnancy and in postpartum these cells acquired ultrastructural features representative of a myofibroblast; for example, a fibronexus and a contractile apparatus were found to be present lying in close contact with the extracellular collagenous and elastic system fibrils. Taken together, these results strongly suggest a contractile function for these cells which might contribute to support of the varying mechanical stresses present during pubic bone movement.

Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes

“…At term, the rupture and rearrangement of helicoidal collagen fibers increase the pliancy and relaxation of the ligament, thereby facilitating parturition in mice (Chihal and Espey, 1973;Crelin, 1969;Hall, 1947;Moraes et al, 2003;Ortega et al, 2001;Pinheiro et al, 2003Pinheiro et al, , 2004Pinheiro et al, , 2005Zhao et al, 1999Zhao et al, , 2000. In addition, the activation of proteolytic enzymes capable of relaxing the symphysis has also been described (McDonald and Schwabe, 1982;Wahl et al, 1977;Weiss et al, 1979).…”

“…Animals Outbred female Swiss mice (90 days old) obtained from the Multidisciplinary Center for Biological Investigation at UNICAMP were mated with males of the same strain, as described by Moraes et al (2003). The presence of a vaginal plug the next morning was considered as day 1 of pregnancy.…”

“…Steroid hormones and relaxin are involved in reproductive tract physiology and help to regulate the processes involved in remodeling of the extracellular matrix (ECM) (for original contributions, see Sherwood, 1994Sherwood, , 2005. Mature chondrocytes released from their lacunae dedifferentiate and become fibroblast-like cells that arrange themselves transversely along the collagen fibers to form a new structure that resembles a true ligament (Crelin, 1969;Moraes et al, 2003). This cell behavior may increase the flexibility of the pubic symphysis in pregnant mice.…”

Estudo morfológico da sínfise púbica de ratos e camundongos durante a gravidez

“…Essas faces cartilagíneas opostas são ligadas por uma lâmina intermédia de fibrocartilagem, cuja espessura varia nos diferentes indivíduos 2,3 . Os ossos e ligamentos pélvicos tornam-se gradativamente mais móveis a partir da décima ou décima segunda semana de gestação, e estas alterações, que facilitam a passagem do feto no momento do parto, são decorrentes da ação de hormônios sexuais, destacando-se a relaxina e a progesterona 4,5 .…”

Estudo morfométrico, ultra-estrutural e imuno-histoquímico do ligamento cruzado cranial com ruptura em cães

“…Em muitas situações fisiológicas e patológicas, alterações marcadas na arquitetura estrutural e bioquímica de fibroblastos e células com fenótipo de fibroblastos têm sido observadas, sugerindo uma forte plasticidade fenotípica permitindo grande adaptação (SCHMITT-GRAFF et al, 1994;MORAES et al, 2004).…”