Interaction of integrin receptors with extracellular matrix is involved in trophoblast giant cell migration in bovine placentomes.

Integrins are heterodimeric glycoproteins involved in cell-cell and cell-extracellular matrix adhesion and signal transduction. We evaluated the distribution and the putative role of integrin receptors and extracellular matrix (ECM) proteins during trophoblast giant cell (TGC) migration and fusion with uterine epithelial cells in the cow. Placentomes from 24 cows, covering day 80 to day 270 of gestation, were used for indirect immunohistochemistry against integrin subunits alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), alpha(6), alpha(v), beta(1), beta(3), beta(4)and ECM proteins collagen type I and IV, fibronectin, laminin. The basement membranes of fetal and maternal epithelia and endothelia were immunoreactive for laminin, fibronectin and collagen IV. Collagens I and IV were found in maternal stroma, while fibronectin was present in fetal and maternal stroma. The integrin subunits alpha(2), alpha(6)and beta(1)were observed in basal aspects of fetal and maternal epithelial and endothelial cells. Additionally, the alpha(6)and beta(1)integrin subunits were colocalized with laminin on TGC. The integrin alpha(2)subunit was also found on TGC, but localized with a strong gradient to the basal side. Cells of the maternal connective tissue, including endothelium, expressed alpha(1), alpha(2), alpha(3), alpha(5), alpha(6), alpha(v), beta(3)and beta(4). The expression of alpha(2), alpha(5), alpha(v), beta(3)and beta(4) occurred mainly in the septal tips. Cells of the fetal mesenchyme were positive for integrin subunits alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), alpha(6), and beta(1). Our results indicate that alpha(2)beta(1)collagen and alpha(6)beta(1)laminin receptors anchor epi- and endothelial cells to basement membranes. We suggest that TGC migrate along a matrix of laminin and maintain cell-cell contact with mononuclear trophoblast cells via alpha(2)beta(1)heterodimers. Integrins in maternal stroma and fetal mesenchyme may be involved in the regulation of proliferation and differentiation of maternal septa and fetal villi.