First Name:
John
Last Name:
Schwabe
Major Department:
Biology
Thesis Director:
Chishimba Mowa
Date of Thesis:
May 2012
Parturition is dependent on complex physical and biochemical changes in the composition and strength of the cervix via a biological process called cervical remodeling. Collagen types I and III comprise nearly 85% of the dry weight of the cervix and are responsible for the tensile strength of the cervix during pregnancy. Changes in the rate of production and degradation of collagen, as well as changes in their extracellular organization, have been identified in late pregnancy and implicated in the changing integrity of the cervix. Understanding these highly complex changes is central to understanding the processes that control cervical remodeling and may require use of complex techniques that simultaneously explore the expression of multiple genes or proteins at a genome-wide scale. We have previously used DNA microarray analysis to delineate vascular endothelial growth factor (VEGF)-regulated genes in the cervix of pregnant rats. However, no studies, thus far, have examined and identified the signature proteins of normal cervical remodeling during early and late pregnancy compared to baseline, i.e., non-pregnant. The purpose of the present study is to profile the pattern of protein expression in the cervices of non-pregnant and pregnant mouse (early and late) in order to elucidate changes in major biological themes (signature proteins) that may be relevant to the mechanisms that underlie cervical remodeling and parturition. Mice cervices from day 0 (ovariectomized), day 11 and day 17 of pregnancy were analyzed by genome-wide proteomics analysis and results will be verified by Western Blot analysis. ANOV A analysis of the proteomics data yielded 73 variably-expressed proteins. Of these, four are directly associated with collagen presence and organization. All four of the collagen-related proteins were present in their highest concentrations during pregnancy, suggesting their involvement in Extracellular Matrix (ECM) changes preceding birth. Of note, we observed that biglycan and lumican, Short Leucine-Rich Proteoglycans (SLRP's) that control the organization and spacing of collagen fibrils, were variably-expressed during pregnancy. The actions of these SLRP's may play an important role in cervical remodeling. Additionally, a number of proteins associated with immune scavenging functions and those associated with cytoskeletal activity were found to be up-regulated during pregnancy when compared to baseline. Based on these data trends, we propose a novel model for the action of biglycan that links both natural and inflammation-mediated preterm birth. These data are important in that they show significant changes in the protein composition of the cervix during pregnancy that were previously uncharacterized and suggest a complex process of ECM reorganization, coupled with a bolstered immune defense, believed to be responsible for causing natural birth.