PARENT SESSION
IMPLANTATION AND PREGNANCY - A

Monday, August 2, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(254) DECIDUA AND AMNION EXPRESS DIFFERENT PROGESTERONE RECEPTOR (PR) ISOFORMS PROFILE, ALL FADED AFTER CONTRACTIONS STARTED.

Shalev, Eliezer^{1, 2}, Weiss, Amir¹, Goldman, Shlomit¹, ¹ HaEmek Medical Center, Afula, Israel² Technion, Haifa, Israel

ABSTRACT- In human, despite the lack of a fall in progesterone levels in the maternal plasma or uterine tissue before the initiation of labor, administration of the PR antagonist RU486 leads to increased uterine activity and induction of labor. Moreover, the use of prophylactic progesterone reduced the rate of preterm delivery. In order to study the theory of functional progesterone withdrawal in human we established a set of experiments examined the expression of PR in all three compartments. Immunohistochemical staining for PR revealed the existence of progesterone receptor in decidua but not in the fetal membranes. More important was the finding of dramatic decline in PR in the decidua after contractions began. Western blot analysis, demonstrate the presence of PR in the decidua obtained from women without contractions, in several isoforms : PR-B , which is the main isoform, PR-A , PR-C , and two other isoforms of 45 and 36 KD. Progesterone (80ug/ml) significantly increased PR-B, PR-C and isoforms 45 and 36 KD by 1.5,2.1, 2.7 and 2.16 fold, respectively (P>0.05). In the decidua obtained from women with contractions, all isoforms of PR sharply decreased or vanish. PR-B and PR-A decreased significantly, by 85.8% and 78.2% respectively (P>0.001). Western blot analysis demonstrates, that before contractions started, PR has several isoforms in the amnion. Amongst PR-C and isoform 36 KD were the main isoforms, while PR-B, PR-A and isoform of 45 KD were detected in low expression. After contractions started, all the PR isoforms sharply decreased or vanish. PR-A significantly decreased 61.9 (P>0.001). No change in PR levels was observed following the addition of 80ug/ml progesterone to the media. In decidua obtained from women without contractions the secretion of ProMMP-2 was significantly decreased (by 21%) in the presence of 80ug/ml Progesterone (P<0.05). In sharp contrast, in the decidua obtained from women with contractions, Progesterone failed to inhibit pro MMP-2 secretion. This study has shown different PR profile between decidua and amnion, which in both compartment declines after contractions began. This may indicate a functional progesterone withdrawal with a decrease in expression of PR-responsive genes in the decidua and amnion leading at the end to increase sensitivity of the tissues to contractile stimuli.

KEY WORDS: Progesterone receptor, progesterone withdrawal, Decidua, Amnion