EXPRESSION OF ADRENOMEDULLIN, A HYPOTENSIVE PEPTIDE, IN THE TROPHOBLAST GIANT-CELLS AT THE EMBRYO IMPLANTATION SITE IN MOUSE

Adrenomedullin (AM) is a newly discovered hypotensive peptide which is believed to play an important role for blood pressure control in the adult. Although it has been well established that a major production s ite of AM is vascular endothelial cells, we now show that AM is most h ighly expressed in trophoblast giant cells, which are derived from the conceptus and are directly in contact with maternal tissues at the im plantation site. Northern blot and in situ hybridization analyses show that the AM mRNA begins to be detected just after implantation and it s level peaks at 9.5 days postconception (d.p.c.) in those cells. Expr ession then falls dramatically after 10.5 d.p.c., coincident with the completion of the mature chorioallantoic placenta. Immunohistochemical analyses show that the AM peptide is secreted from the trophoblast gi ant cells into the surrounding tissues, i.e., embryo, decidua, and mat ernal circulation. In contrast, the expression of an AM receptor was n ot detected by Northern blot analyses in either embryo or trophoblast giant cells at 7 d.p.c., when the AM gene is most highly expressed in the trophoblast giant cells. This suggests that the AM produced and se creted from the embryo's trophoblast giant cells acts on the maternal tissues rather than on the embryonic tissues. Based on these results, we propose that the high production of AM may be the mechanism by whic h the embryos survive at the early postimplantation period by pooling maternal blood in the implantation site in order to secure nutrition a nd oxygen before the establishment of efficient embryo-maternal circul ation through the mature placenta. (C) 1998 Academic Press.