Homodimeric pregnancy-associated plasma protein-A in normal human placenta of first and third trimester of pregnancy: Biochemical and morphological observations

Insulin-like growth factors (IGFs) become bio-available following hydrolysis of binding proteins by homodimeric PAPP-A (dPAPP-A); this is a metzincin associated with the membranes of trophoblast phenotypes, the precise placental localization of which was unknown. Our study on placental samples of the first trimester shows the immunohistochemical localization of proMBP and dPAPP-A in the same cells. In contrast, dPAPP-A is mainly negative in the syncytium (ST) and positive in the villous cytotrophoblast (VCT) while htPAPP-A is strongly expressed in the ST and negative in the VCT at term, suggesting a progressive deactivation of the enzyme with gestational age. In agreement with the above, dPAPP-A is released only by first trimester placental explants in culture.