The modulation of decidual cells proliferation and differentiation by progesterone and prostaglandins

The ability of prostaglandins and progesterone to modulate the rate of DNA synthesis and the differentiation of endometrial cells into polyploid decidual cells was studied in vivo and in vitro. Intraperitoneal administration of indomethacin (5 mg/kg), an inhibitor of PG synthesis, on the 3rd or 4th day of leukocytic vaginal smear (day L3 or L4, respectively), but not on the 5th day (L5), suppressed the induction of deciduomata in vivo. The injection of indomethacin to pseudopregnant rats on day L3 had no effect on the rate of DNA synthesis by endometrial cells which were explanted from the uterus on day L4. Indomethacin and other inhibitors of PG synthesis, such as flufenamic acid, cortisol, and progesterone had a stimulatory effect on the rate of DNA synthesis when added to cultures of cells explanted from deciduoma on day L5. PGE2 (5-10 micrograms/ml) inhibited DNA synthesis in control, indomethacin-treated and progesterone-treated L5 cell cultures. Inclusion of indomethacin in the culture medium during enzymatic dissociation of endometrial cells and during the subsequent culture of the cells for four days, did not prevent the appearance of polyploid and multinucleated decidual cells. In vivo administration of indomethacin (5 mg/kg, i.p.) on day L3 or on day L4 (3 h before collecting the endometrial cells), reduced the incidence of polyploidy in the 4-day cultures. This effect of indomethacin could be prevented in endometrial cells (harvested 3 h but not 24 h after treatment with the drug) by the addition of progesterone. These results suggest that: (1) the cooperation between prostaglandins and progesterone at the late sensitization period of the uterus may lead to a programmed expression of polyploidization during the 4-day culture; and (2) the rate of DNA synthesis in the deciduoma at the proliferation phase may be influenced by steroid-induced changes in PGE content of the tissue.