Different regulation of tissue inhibitors of metalloproteinases-1, -2 and -3 in human endometrial stromal cells during decidualization in vitro.

Aim:  Endometrial tissue inhibitors of metalloproteinases (TIMPs) appear to play an essential role during early implantation by modulating the invasiveness of the trophoblast. The expression of TIMP-1, TIMP-2 and TIMP-3 in human endometrial stromal cells (ESC) was investigated during decidualization in vitro. Methods:  Endometrial stromal cells were isolated from hysterectomy specimens from premenopausal women undergoing surgery for benign reasons. Decidualization in vitro was induced by the application of 1 µmol/L progesterone and 30 nmol/L 17β-estradiol over 9 days. The expression of TIMP-1, TIMP-2 and TIMP-3 in ESC was measured by semiquantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay over intervals of 3 days. Results:  Decidualization in vitro was confirmed by a significant increase in prolactin expression. TIMP-1 and TIMP-2 mRNA and secreted protein showed no significant changes over the time-course of decidualization. In contrast, TIMP-3 was upregulated during the first 3 days of decidualization. An eightfold upregulation was observed until day 6, and the effect was less pronounced by day 9. Conclusion:  These results suggest a regulatory role of the TIMP system for endometrial differentiation in the second half of the menstrual cycle and in early implantation. The expression pattern of endometrial TIMP-3 might be important for the regulation of trophoblast invasion. (Reprod Med Biol 2008; 7: 169-175).