Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia

Objective To investigate the alterations of syncytin, a fusogenic membrane protein involved in syncytiotrophoblastic layer formation, and its receptor ASCT2 expression in placental development and pre-eclampsia. Design Analyses of syncytin and ASCT2 expression in placentas from different stages of pregnancy and women with pre-eclampsia and in cytotrophoblasts cultured in normoxic and hypoxic conditions. Setting Placental samples were collected from a tertiary medical centre. Population Sixteen women with pre-eclampsia and 58 pregnant women presented as pregnancy (5-19 weeks of gestation) for elective termination, preterm birth, or normal term delivery. Methods The quantitative real-time polymerase chain reaction was used to study the syncytin and ASCT2 expression during placental development in 35 placentas from women without pre-eclampsia (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic placentas (n=16) compared with gestational-age-matched controls (n=16). Western blot analysis was performed to study the protein level of syncytin in pre-eclamptic placentas and gestational-age-matched controls. The hypoxic effect on trophoblastic syncytin and ASCT2 expression was further studied in cytotrophoblasts cultured in 2% oxygen (n=7). Main outcome measures Syncytin and ASCT2 messenger RNA ( mRNA) in placental tissue and cytotrophoblasts. Results The level of syncytin mRNA expression increased significantly since the first trimester of pregnancy until 37 weeks of gestation, when the level of syncytin expression was reduced. The ASCT2 mRNA expression was decreased significantly since the second trimester and was relatively stable since then to 40 weeks of gestation. Furthermore, a significant reduction in syncytin mRNA expression was observed in pre-eclamptic placentas and cytotrophoblasts cultured in hypoxia, but not a reduction in ASCT2 mRNA expression. Correlatively, the protein level of syncytin was decreased in pre-eclamptic placentas. Conclusions A reduced placental expression of syncytin but not ASCT2 may contribute to altered cytotrophoblastic cell fusion processes and disturbed placental function in pre-eclampsia. Correspondingly, hypoxia decreases syncytin but not ASCT2 gene expression in cultured cytotrophoblasts.