Progesterone-regulated determinants of stromal cell survival and death in uterine decidua are linked to protein kinase C activity

This study examined the role of protein kinase C enzymatic activity as a ph ysiologic determinant of stromal cell death in decidua basalis (DB) during pregnancy. The expression of epidermal growth factor receptor (EGF-R) and B cl2 was used as an indicator of stromal cell proliferation/survival, wherea s Bar and the occurrence of apoptosis provided an index of cell death. Stro mal cell cycle progression during pregnancy and after in vivo administratio n of phorbol esters was analyzed by flow cytometry. DB were isolated from p regnant rats between Days 8 and 21 of pregnancy and prepared for immunohist ochemistry, Western blotting procedures, or how cytometry. The results show ed that stromal cells were actively proliferating on Days 8 and 10, whereas the frequency of cell death by apoptosis increased progressively between D ays 14 and 21 (Day 22 is term). The proliferative stage was characterized b y low PKC activity and high levels of EGF-R and Bcl2 expression. On the oth er hand, DB regression (Days 14-21) was marked by an elevation in endogenou s PKC activity and Bar expression; EGFR and Bcl2 were suppressed. Administr ation of phorbol 12-myristate, 13-acetate (0.4 mu mole/kg) induced apoptosi s on Day 10. Additionally, antiprogestin (RU-486) given on Day 9 induced PK C activity and Bar expression within 6 h and suppressed Bcl2 and EGF-R. By 12 h, RU-486 enhanced percent apoptotic cells. Thus, enhanced levels of PKC activity were closely linked to stromal cell apoptosis. (C) 1999 Elsevier Science Inc. All rights reserved.