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Submitted on June 24, 2004
Accepted on October 12, 2004
Department of Molecular and Integrative Physiology (H.L., S. Z., O.D.S.) and College of Medicine (O.D.S.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; and Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine (P.A.F.), Mobile, Alabama 36688
* To whom correspondence should be addressed. E-mail: od-sherw{at}uiuc.edu.
Relaxin promotes marked growth of the cervix during the second half of rat pregnancy, and this growth is accompanied by an increase in both epithelial and stromal cells. The objective of this study was to test the hypothesis that the extent to which relaxin promotes proliferation and inhibits apoptosis of cervical cells is greatest during late pregnancy in rats. The influence of neutralization of circulating relaxin by iv injection of 5 mg of monoclonal antibody against rat relaxin (MCA1) was examined at three-day intervals throughout the second half of pregnancy. Controls were injected with either 5 mg of monoclonal antibody against fluorescein or 0.5 ml PBS vehicle. To evaluate cell proliferation, 5'-bromo-2-deoxyuridine was injected sc 8 h before cervices were collected. Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick end-labeling and electron microscopy were used to detect apoptotic cells.
Neutralization of relaxin with MCA1 decreased the rate of proliferation and increased the rate of apoptosis of cervical cells by day 13. However, the extent to which relaxin influenced these processes was greatest and dramatic by late pregnancy. In MCA1-treated rats on day 22 of pregnancy, the rates of proliferation of both epithelial and stromal cells were less than 20% those in controls, and the rates of apoptosis in epithelial cells and stromal cells were more than 10-fold and 3-fold, respectively, greater than those in controls.
In conclusion, this study provides evidence that the extent to which relaxin promotes proliferation and inhibits apoptosis of cervical epithelial and stromal cells is greatest during late pregnancy.
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