Possible Role of Integrins in Cervical Ripening During Late Pregnancy

Integrins are αβ heterodimeric transmembrane proteins. Integrins mediate cytoskeletal interactions at the inner face of the membrane and attach to extracellular matrix (ECM) at sites of cell substratum or cell-cell interaction to mediate adhesion, events. The biological functions of integrins include cell adhesion, cell spreading, cytoskeletal organization, cell migration, matrix assembly, and signal transduction. The extracellular matrix is composed of a variety of proteins (collagen, elastin), and ground substance (proteoglycans, glycosaminoglycans) to form a meshwork surrounding stromal cells. Functions of the extracellular matrix include not only support but also include regulation of cell division, adhesion, cell motility, migration, and differentiation during embryonic development. Pregnancy involves both histological and biochemical changes in the cervix. Experimental evidence indicates that a variety of biochemical changes occur in the cervix during late pregnancy. These changes include increased hyaluronic acid concentration, collagen solubility and collagenase concentration. The vascularity of the cervix also increases. Dermatan sulfate concentration and collagen concentration decrease. Histological changes include collagen fibers becoming dispersed and disorganized; luminal epithelium undergoes stratification and folding, and becomes more vacuolated. It has reported that α1βI integrins induce downregulation of collagen gene expression and α2β I integrins mediate the induction of matrix metalloprotien-1 (collagenase). Recent studies indicate that collagenases are responsible for the degradation and loss of collagen fibers involved in the process of ripening and dilatation of the cervix in late pregnancy. These studies suggest that the integrin β1 subunits that bind to the cytoskeleton contain tyrosine phosphorylation sites. Tyrosine phosphorylation triggers several intracellular signaling protein complexes to transducer the signals into the cell interior. These signals can control gene expression in target cell, and change the cell\u27s behavior. Therefore, we hypothesized that integrin βI subunits might regulate gene expression that influences histological and biochemical changes in the cervix during late pregnancy. In this thesis, we report that the mRNA for integrin β1 subunits was expressed at a higher level in late pregnant rats, compared with non-pregnant rats based on Northern blot analysis. The probe used for the Northern blots was a cDNA for rat integrin β1 subunit, encoded from a rat cerebral cortex oligodendroglia cDNA library, amplified by the polymerase chain reaction (PCR). The cDNA probes were labeled nonisotopically and hybridized with cervical mRNA on nylon membranes. This experiment indicates integrin βI subunits may play an essential role in biochemical and histological changes associated with cervical ripening in rats