Progesterone and estrogen regulation of rat decidual cell expression of proliferating cell nuclear antigen

This study was an examination of the role of progesterone (P4) and estradiol-17beta (E2) as stromal cell mitogens in the decidua basalis (DB) of the rat during pregnancy. Pregnant rats were ovariectomized (Ovx) on Days 8 and 12 of pregnancy, treated with P4, E2, or both, and killed on Days 10 and 14, which correspond to times of stromal cell proliferation and regression, respectively. In some experiments, rats received pellets of the anti-progestin RU-486 on Day 9 and were killed 6, 12, and 24 h later. The mitotic index (MI) and in situ image analysis of expression of proliferating cell nuclear antigen (PCNA) were used to assess cell cycle progression. Highest expression of PCNA occurred on Days 8-12 of pregnancy, and MI was maximum; MI became zero and PCNA expression decreased dramatically thereafter (i.e., Days 14, 17, 21). Percentage of cells expressing intense PCNA on Day 10 (40%) declined to 5% after Ovx and Ovx + E2 (p < 0.05), whereas Ovx + P4 maintained PCNA. By Day 14, only 1% of stromal cells expressed intense PCNA, which was not significantly altered by Ovx, Ovx + E2, or Ovx + P4 but increased after Ovx + P4 and E2 (p < 0.05). By 6 h of RU-486, MI declined 3-fold, and intense PCNA expression was essentially lost. These changes preceded loss of histological integrity of the DB. Cells with undetectable PCNA steadily increased from 8% at 6 h to 28% by 24 h (p < 0.05). Thus RU-486 appeared to block cell cycle progression and enhanced PCNA turnover. P4 was essential for stromal cell proliferation during early pregnancy (Days 8-10), but this action was lost by Day 14.