Human trophoblast invasion and spiral artery transformation: the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction

Abstract

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance. Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR); these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR. We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.

Figure 1.

Western blot analysis of placental villous tissue to validate the PECAM-1 antibody. 1 and 2 represent two different term placentas.

Figure 2.

Double immunofluorescence for PECAM-1 (red) and cytokeratin (green) of a placenta at 38 weeks of gestation (A), a cell column at 16 weeks of gestation (B), and a cell island at 8 weeks of gestation (C). ABC method for PECAM-1 immunostaining in 38-week placenta (D), a cell column (E: left, cytokeratin; right, PECAM-1), cell island (F: left, cytokeratin; right, PECAM-1) and basal plate (G: lower panel, cytokeratin; upper panel, PECAM-1). H and I: Cytokeratin immunostaining (left) and PECAM-1 immunostaining (right) in myometrium and decidua respectively at 9 weeks of gestation. Double immunofluorescence for cytokeratin (J), PECAM-1 (K), and both (L) in a myometrial spiral artery at 18 weeks of gestation.

Figure 3.

Double immunofluorescence staining a placental bed biopsy obtained from a normal pregnancy (A–C), a pregnancy complicated by PE (D–F), and a pregnancy complicated by FGR (G–I). A, D, and G: Cytokeratin immunostaining. B, E, and H: PECAM-1 immunostaining. C, F, and I: Simultaneous detection of cytokeratin and PECAM-1 immunostaining.