LOCALIZATION OF ENDOGLIN, A TRANSFORMING GROWTH-FACTOR-BETA BINDING-PROTEIN, AND OF CD44 AND INTEGRINS IN PLACENTA DURING THE FIRST TRIMESTER OF PREGNANCY

Endoglin is an integral membrane glycoprotein that binds transforming growth factor-beta 1 (TGF beta 1) with high affinity and is predominan tly expressed on human endothelial cells. Characterization of this hom odimeric protein from human term placenta has shown that it is particu larly abundant on the syncytiotrophoblast. Immunofluorescence staining of sections of first trimester placenta now reveals that endoglin is found at even higher levels on the syncytiotrophoblast of samples rang ing from 6 to 12 wk of gestation. Very low levels are observed on the undifferentiated cytotrophoblast cells that can be identified by their expression of the a6 beta 4 integrin, a receptor for laminin. Within the villi, blood vessels and stromal cells are negative for endoglin b ut positive for alpha 1 beta 1 integrin, a receptor for collagens and laminin. Stromal cells also express CD44, a hyaluronic acid receptor. Of particular interest is the up-regulation of endoglin expression in the transition from polarized undifferentiated to non-polarized interm ediate cytotrophoblasts (CTB) as the cells align in columns to invade the uterus. This occurs in parallel with the acquisition of alpha 5 be ta 1 integrin (fibronectin receptor) and precedes the loss of alpha 6 beta 4 integrin. CD44 and alpha 1 beta 1 integrin are noticeably absen t from the CTB within the columns but are expressed at very high level s throughout the placental bed. Endoglin is undetectable within the de cidua; thus, intermediate CTB that have invaded the placental bed expr ess alpha 5 beta 1 integrin and cytokeratins but not endoglin. Our stu dies suggest that the expression of the TGF beta binding protein endog lin is critical to placental development. It is low on CTB, transientl y increased on intermediate trophoblast cells within the columns, and induced and maintained at high levels on syncytiotrophoblast throughou t pregnancy.