The Expression of PDGF α-and β-Receptors in Subpopulations of PDGF-Producing Cells Implicates Autocrine Stimulatory Loops in the Control of Proliferation in Cytotrophoblasts that Have Invaded the Maternal Endometrium

Abstract

In order to explain the high proliferative potential of human placental cytotrophoblasts, we have addressed the potential involvement of platelet-derived growth factor (PDGF) ligand and receptors. Although PDGF is usually described as a mitogen for cells of mesenchymal origin, we show in this report that extra-villous term placental cytotrophoblasts express the PDGF α-and β-receptor genes, both in vivo and in vitro. In addition, cytotrophoblasts produce significant amounts of PDGF-B protein. By immunohistochemical analysis of receptor expression, we found that the PDGF a-receptors could be detected at the cell surface, while the PDGF β-receptors were only detected inrracellularly. In addition, double immunostaining analysis showed that the PDGF α-and β-receptor molecules are expressed in different subpopulations of cytotrophoblasts. The addition of PDGF-AA and PDGF-BB homodimers to cytotrophoblast primary cultures induced a significant increase in DNA synthesis. We conclude, therefore, that PDGF is a growth factor for placental cytotrophoblasts and suggest that the growth of cytotrophoblasts can partly be explained by a PDGF autostimulatory loop, limited by the number of receptor-positive cytotrophoblasts.

Key Words:

• PDGF
• platelet-derived growth factor
• in situ hybridization
• cytotrophoblasts
• placenta