Myofibroblast Differentiation in the Connective Tissues of the Amnion and Chorion of Term Human Fetal Membranes—Implications for Fetal Membrane Rupture and Labour

Abstract

An area of the fetal membranes, within the rupture tear after spontaneous delivery at term, exhibits altered morphology compared to more distal sites. It is characterized by marked swelling of the amniotic and chorionic connective tissue layers, consistent with structural weakness, and a marked reduction of the thickness of both the cytotrophoblast and decidual layers. These features, albeit less extreme, have been identified in fetal membranes in the lower uterine pole in patients prior to labour. In this study of pre-labour, labour-affected and post-labour term fetal membranes, we report that these regions are associated with an alteration in the phenotype of the vimentin positive mesenchymal cell population of the chorionic connective tissue reticular layer, and are consistent with myofibroblastic differentiation, i.e. α-smooth muscle actin (α-sma) expression. In the reticular layer of the lower uterine pole biopsies in the labour-affected group the numbers and densities of α-sma immunoreactive positive cells were 17-fold (P=0.04) and 8.5-fold (P=0.02) higher than in mid-zone biopsies. After delivery, in rupture line biopsies the numbers and densities were 50-fold (P=0.002) and 36-fold (P=0.003) higher compared to mid zone biopsies. The percentage of the vimentin positive population positive for α-sma was 2–5 per cent in mid-zone biopsies compared to 49 per cent (P=0.03) in the labour-affected ‘cervical’ biopsies and 69 per cent (P=0.05) in the rupture line biopsies. Within the tear sites, α-sma positive cells were also detected within the fibroblastic layer of the amniotic connective tissue. Although there was no significant difference between the numbers and density of α-sma cells in the reticular layers between mid and lower uterine pole biopsies in the pre-labour group, in a proportion of patients the biopsies were similar to labour-affected biopsies indicating that this alteration occurs prior to clinically apparent labour in these patients. The incidence of α-sma positive cells in the reticular layer correlated with morphological changes within the fetal membranes, for example thickness of reticular (r2=0.349, P=0.0006) and amniotic connective tissue layers (r2=0.389, P=0.0002). This suggests that cellular activities associated with myofibroblastic differentiation in the reticular layer of the chorion may be associated with the observed connective tissue changes, fetal membrane rupture and labour.