Pre-eclampsia (PE) is a pregnancy complication associated with abnormal formation of the placenta. To date, most studies of PE have focussed on cytotrophoblasts (CTBs) within the villous placenta (the chorion frondosum); the deficient invasion of these cells into the uterine wall is thought to lead to abnormal placentation and hence PE. Here, on p. 767, Susan Fisher and colleagues reveal that CTBs within a different region of the human placenta – the smooth chorion – are implicated in severe PE. They first report that the CTB layer in the smooth chorion is expanded in severe cases of PE and is less organised. These morphological changes are accompanied by changes in the expression profiles of smooth chorion CTBs. In particular, smooth chorion CTBs exhibit enhanced expression of HLA-G, integrin α4 and E-cadherin, all of which are factors that extravillous CTBs normally modulate as they invade the uterine wall. The researchers further show that severe PE is associated with global gene expression changes in smooth chorion CTBs that are distinct from the transcriptional responses of villous and extravillous CTBs to severe PE, which they previously described. Overall, these findings suggest that smooth chorion CTBs play a greater role in placentation and pregnancy outcome than previously appreciated.
