Regulation of human trophoblast proliferation and apoptosis during pregnancy.

In order to elucidate the regulation of human placental growth during pregnancy, we have assessed PCNA expression, apoptosis and Bcl-2 protein expression in placental trophoblasts over the course of pregnancy. PCNA, Bcl-2 protein and Fas antigen expression were examined by the avidin/biotin immunoperoxidase method, while apoptosis was assessed by in situ DNA 3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were noted in cytotrophoblasts (C-cells), being most abundant in very early placenta, less abundant in midterm placenta and least abundant in term placenta. In contrast, Bcl-2 protein expression was noted in syncytiotrophoblasts (S-cells), being least abundant in very early placenta, less abundant in midterm placenta and most abundant in term placenta. These results indicate that very early placenta is characterized by highly proliferative activity of C-cells associated with increased occurrence of apoptosis. Since Bcl-2 protein is an apoptosis-inhibiting gene product, the minimal occurrence of apoptosis in term placenta seems likely to be attributable to the increased expression of Bcl-2 protein in S-cell in term placenta. On the other hand, in extravillous trophoblasts on cell columns, both PCNA and Bcl-2 protein expression were pronounced only in the shallower part, while Fas/Fas ligand expression and apoptosis were prominent in the deeper part. Thus, it seems likely that Bcl-2 protein expression also participates in the regulation of extravillous trophoblast apoptosis.