Expression of Endogenous Retrovirus ERV-3 Induces Differentiation in BeWo, a Choriocarcinoma Model of Human Placental Trophoblast

Abstract Differentiation-related expression of endogenous retrovirus ERV-3 env in the normal human placental syncytiotrophoblast suggests a role in placental development. The choriocarcinoma cell line BeWo, a model of trophoblast differentiation, is maintained in an undifferentiated state and undergoes differentiation upon the addition of forskolin. The expression of ERV-3 env mRNA increased after 48 h forskolin treatment, concurrently with increased intercellular fusion and production of human chorionic gonadotropin (β-hCG) mRNA, a hormonal differentiation marker for trophoblast. Over expression of ERV-3 env induced differentiation of BeWo characterized by decreased cell growth, differentiation-related morphologic changes, and induction of β-hCG mRNA. These results support the first known role for the expression of an endogenous retrovirus in trophoblast differentiation.