Decreased expression of Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia

Abstract

Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) is a protein that mediates actin cytoskeletal reorganization and lamellipodia protrusion formation, which are required for cell migration and invasion. The primary purpose of this study was to determine whether there is an association between reactive oxygen species (ROS) and WAVE2 in pre-eclampsia, and whether WAVE2 expression in trophoblast cells is vulnerable to oxidative stress. This study observed excessive generation of ROS and decreased expression of WAVE2 in pre-eclamptic placentas compared with normotensive controls. Moreover, there was a significant negative correlation between ROS and WAVE2 protein in pre-eclamptic placenta (P<0.001). An in-vitro model of hypoxia–reoxygenation (H/R) was used to imitate oxidative stress in placental trophoblasts, and it was found that the expression of WAVE2 protein in trophoblasts was decreased after H/R treatment. Additionally, compared with normoxia, decreased cell proliferation, higher cell apoptosis and attenuated cell migration and invasion were detected in trophoblasts exposed to H/R. In conclusion, the findings strongly suggest that excessive oxidative stress can decrease WAVE2 expression in trophoblasts and that the decreased expression of WAVE2 in trophoblast cells may be involved in the development of pre-eclampsia.It is postulated that pre-eclampsia is due to shallow trophoblast invasion and insufficient remodelling of uterine spiral artery. Oxidative stress, resulting in over-production of reactive oxygen species (ROS), plays an important role in this process. However, the way that placental oxidative stress results in the reduced trophoblasts invasion and migration remains enigmatic. WAVE2 is a protein that mediates actin cytoskeletal reorganization and lamellipodia protrusion formation which are required for cell migration and invasion. We observed excessive generation of ROS and decreased expression of WAVE2 in pre-eclamptic placentas compared with normotensive controls. Moreover, there was a significant negative correlation between ROS and WAVE2 protein in pre-eclamptic placenta. We utilized an in-vitro model of hypoxia–reoxygenation (H/R) to imitate oxidative stress in placental trophoblasts, and we found that the expression of WAVE2 protein in trophoblasts was decreased followed by H/R treatment. Additionally, compared with normoxia condition, decreased cell proliferation, higher cell apoptosis and attenuated cell migration and invasion were detected in trophoblasts exposed to H/R. Our findings highlight that decreased WAVE2 expression is associated with oxidative stress and, thus, may be involved in the pathogenesis of pre-eclampsia.