LOCALIZATION OF AMPHIREGULIN IN THE HUMAN PLACENTA AND DECIDUA THROUGHOUT GESTATION - ROLE IN TROPHOBLAST GROWTH

Amphiregulin (AR) is a growth regulatory glycoprotein with significant amino acid homology to members of the epidermal growth factor (EGF) f amily. Its effects ave mediated via the EGF receptor tyrosine It kinas e or through specific nuclear targeting sequences. In this study, the localization of immunoreactive AR was examined in paraformaldehyde-glu taraldehyde fixed, paraffin-embedded human placentae and decidua obtai ned at various stages from 11 weeks to term pregnancy using the avidin -biotin complex/peroxidase method. In addition, the effects of AR on t rophoblast proliferation mere evaluated fi om (3)HTdR uptake by first trimester human trophoblast cells. Results revealed immunolocalization of AR to the nucleus as well as the cytoplasm of the syncytiotrophobl ast cell layer of chorionic villi until approximately meek 18 of gesta tion after which no immunostaining mas detected. Villous and extravill ous cytotrophoblast cells as well as decidual tissue mere negative for AR at all gestational ages examined. In the presence of exogenous AR, there was a dose-dependent dependent increase in proliferation of the trophoblast at AR concentrations ranging from 1-100 ng/ml. These resu lts suggest that AR may be an important paracrine or juxtacrine growth stimulatory molecule for cytotrophoblast cells in situ early;ly in ge station.