Regression of the decidualized mesometrium and decidual cell apoptosis areassociated with a shift in expression of Bcl2 family members

The purpose of this study was to determine whether regression of the decidu a basalis (DB), which begins on Day 14 of pregnancy in the rat, results fro m an intrinsic program of apoptosis regulated by Bar and Bcl2. Expression o f Bar and Bcl2 and the incidence of apoptosis were evaluated throughout ges tation by Western blot analysis and detection of DNA fragments. Antiprogest in (RU486) was also administered during proliferation of DB to study proges terone regulation of Bax/Bcl2 balance. Bar, the pro-apoptotic protein, was expressed at a low level throughout pregnancy, whereas Bcl2, the pro-surviv al partner, was most abundantly expressed on Days 8 and 10, which are a tim e of proliferation and decidualization, and declined to barely detectable l evels thereafter. These changes resulted in a 12-fold increase in the Bax:B cl2 ratio on Day 17 as compared with Day 8 of pregnancy (P < 0.05). DNA lad dering and in situ staining of DNA fragments first became visible on Day 14 and involved 2% of cells by Days 17 and 21 (P < 0.05). Treatment with RU48 6 on Day 9 enhanced Bar and suppressed Bcl2 within 6 h, increasing the Bax: Bcl2 ratio sixfold (P < 0.05). Apoptosis was minimal at 6 h and increased t o 9% of cells by 24 h (P < 0.05). Thus, progesterone appears to regulate th e apoptotic threshold of stromal cells by modulating Bar and Bcl2 expressio n.