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The Effects of Blocking the Actions of Estrogen and Progesterone on the Rates of Proliferation and Apoptosis of Cervical Epithelial and Stromal Cells During the Second Half of Pregnancy in Rats¹

Department of Molecular and Integrative Physiology³ College of Medicine,⁴ University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Serum levels of the ovarian hormones relaxin, estrogen, and progesterone are elevated during the second half of 23-day rat pregnancy when dramatic growth of the cervix occurs. Recently, we demonstrated that relaxin contributes to cervical growth by both promoting cell proliferation and inhibiting apoptosis of cervical cells during late pregnancy. The objective of this study was to determine the influence of estrogen and progesterone on the rates of proliferation and apoptosis of cervical cells at 3-day intervals during the second half of rat pregnancy. The actions of estrogen and progesterone were blocked with s.c. injections of estrogen antagonist ICI 182,780 and progesterone antagonist RU486, respectively. To evaluate cell proliferation, 5'-bromo-2'-deoxyuridine was injected s.c. 8 h before cervixes were collected. Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick end-labeling was used to detect apoptotic cells. Proliferating and apoptotic cells were identified by immunohistochemistry, and the rates at which these processes occurred were determined by morphometric analysis. Blocking the actions of estrogen and progesterone decreased the rates of proliferation and increased the rates of apoptosis of both cervical epithelial and stromal cells during late pregnancy. However, blocking the actions of progesterone had the opposite effects on apoptosis of both cervical epithelial and stromal cells during the middle of pregnancy. In conclusion, this study provides evidence that estrogen and progesterone, like relaxin, contribute to the increase in the cervical cell content during late pregnancy by promoting proliferation and inhibiting apoptosis of cervical cells.

apoptosis, cervix, estradiol, pregnancy, progesterone

² Correspondence: O. David Sherwood, Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801. FAX: 217 333 1133; od-sherw{at}uiuc.edu

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