Syncytin induced cell fusion and apoptosis associated with placental dysfunction in patients with preeclampsia and IUGR

Abstract

Complications of pregnancy like preeclampsia (PE), HELLP-syndrome or intrauterine growth restriction (IUGR) are associated with abnormal placentation. In early pregnancy cytotrophoblasts (CT) fuse and form multinuclear syncytiotrophoblasts (SCT). The envelope gene of the human endogenous retrovirus (HERV)-W, Syncytin is expressed in SCT and mediates CT fusion. Apoptosis is crucial to development and homeostasis of the placenta, but the mechanism of apoptosis in CT is unknown. The aims in this investigation were to define clinical parameters associated with PE, HELLP and IUGR and study the process of cell fusion and apoptosis in placental tissue and in cultured CT compared to controls. Placental tissue showed a reduction in Syncytin expression in PE/IUGR (5.4-fold, p=0.047) and HELLP/IUGR (10.6-fold, p=0.019). Cultured CT were decreased in Syncytin copy numbers to 4.9-fold in PE/IUGR (p=0.025) and 130-fold in HELLP/IUGR (p<0.001). ß-hCG secretion was reduced in cultured CT from patients with PE (3.4-fold, p=0.013) and HELLP (16.4-fold, p=0.001). In contrast, placentas showed a higher rate of apoptosis in PE (1.8-fold, p=0.04) and HELLP (1.9-fold, p=0.008). Increased apoptosis was also confirmed in cultured CT. Therefore, both primary and cultured CT from PE or HELLP had a higher apoptosis rate and significantly lower expression levels of Syncytin. The finding of abnormal Syncytin expression may alter the normal process of cell fusion and formation of SCT. The higher rate of apoptosis may contribute to the development and severity of these pregnancy complications.