Thrombopoietin modulates the proliferation, migration and cytokine profile of decidual cell subsets during early gestation.

During early gestation, a considerable increase in different leukocyte subsets can be observed in the decidualized endometrium concomitantly to the invasion of cytotrophoblast cells (CTB). To date, it is still in question which factors induce this accumulation of immune cells and whether it is evoked by an in situ proliferation or by a migratory process. Studies on hepatoblastoma cells identified thrombopoietin (TPO) as a novel factor, which elicits dose-dependent chemotactic and chemokinetic effects. However, the impact and function of TPO on decidual cells has not been clarified yet. This study analyses the expression and function of TPO and its receptor c-Mpl in decidua during early gestation. Applying western blot analysis, we detected that TPO is expressed by decidual immune cells (uNK cells and CD14+ monocytes) as well as CTB and decidual stromal cells (DSCs). Expression of the different isoforms of c-Mpl was found in uNK cells, CD14+ monocytes and DSC. Studying the signalling pathway proteins in the uNK cells, an activation of STAT3/Tyr by TPO, was detected. The investigation of the proliferative effects of TPO on the decidual cell subsets revealed that TPO enhances the proliferation of uNK cells and CTB. No change of the proliferative activity after TPO incubation was found in DSC and even a decrease in CD14+ monocytes. In addition, TPO was observed to induce significantly the migratory activity of uNK cells, CD14+ monocytes and CTB. Investigating the effects of TPO on the cytokine profile of the isolated decidual cells, we observed a decrease in the secretion of IL-8, IL-10 and IL-1β of isolated uNK cells, CD14+ monocytes and CTB, although these changes did not reach statistical significance. Thus, we here identified TPO as a novel factor modulating the proliferation, migration and possibly cytokine secretion of decidual cell subsets.