Expression and localization of αvβ6 integrin in extraplacental fetal membranes:: possible role in human parturition

Successful outcome of human parturition is dependent upon extensive remodelling of the extracellular matrix (ECM) of the cervix, uterus and fetal membranes, a process that involves adhesion molecules and is also common in tumour invasion and metastasis. To elucidate the role of integrins in human parturition, this study characterizes the expression of the tumour-associated alpha(v)beta(6) integrin in human placenta and extraplacental membranes. Immunohistochemical analysis of the placenta and fetal membranes from normal vaginal deliveries (NVD) (n=10) exhibited strong intensity of staining for alpha(v)beta(6) integrin (3=dark brown) in the epithelial layer of the amnion. Weak immunohistochemical staining of alpha(v)beta(6) integrin (1=pale brown) was detected in the chorion and at the decidual edge. These results were consistent with the immunodetection of alpha(v)beta(6) integrin by western blot analysis that showed 4-fold enhanced expression in the amnion compared to chorion of both NVD and term elective caesarean section (CS) deliveries. Even though there was no difference in the extent of immunohistochemical staining of alpha(v)beta(6) integrin between the amnion of NVD and CS groups, significantly higher intensity of staining was observed in the NVD amniotic epithelium compared to that of CS (n=10) (chi(2)=10.25, P=0.0059). Western blot analysis of the fetal membranes showed no differences in the expression of alpha(v)beta(6) integrin between the NVD and CS groups. Gelatin zymography demonstrated the presence of pro-matrix metalloprotein-9 (MMP-9) and pro-MMP-2 in the amnion and chorion of NVD, whereas in CS only the presence of pro-MMP-2 was observed. These results suggest that in term pregnancy, human fetal membranes express alpha(v)beta(6) integrin and that the expression is significantly higher in amnion compared to chorion. The fact that enhanced expression of alpha(v)beta(6) integrin in fetal membranes correlates with the expression of pro-MMP-9 in NVD is consistent with the invasive role of the integrin in cancer and suggests that the molecule may have a proteolytic role in the initiation and progression of labour.