Interferon Inhibits Trophoblast Fusion and Contributes to Male-female Dimorphism at Mouse Placenta During Maternal Immune Activation

Abstract

The placenta is a temporary organ that forms in the uterus during pregnancy, which provides nutrients to the fetus and works as a barrier that separates the maternal and fetal circulations. Maternal immune activation during gestation is associated with adverse outcomes in offspring1. Studies using rodent models suggest that inflammatory responses at the placenta contribute to growth restriction and even fetal demise2,3. The unpublished data from our lab shows that during maternal immune activation (MIA) induced by poly(I:C), the permeability of the maternal fetal barrier increased and a significant higher of permeability has been found in male-associated placentas compared to female-associated ones. In this thesis, I found that the basal Interferon-Stimulated Gene (ISG) expression in male-associated placentas is lower than female-associated placentas. During MIA, however, ISG expression in male-associated placenta significantly increased while it remained almost the same in female. Trophoblast is the main cell type that makes up the maternal-fetal barrier at the placenta. Some subtypes of these cells undergo intercellular fusion and form syncytia. Using Bewo cell line as an in vitro model for trophoblast fusion, I found that IFNβ and IFNγ significantly inhibited the Bewo cell fusion, which provides a possible explanation for placental permeability increase in MIA as well as the male-female dimorphism. Taken together, our study suggests that reduced syncytia formation caused by interferon responses could contribute to the increase of placental permeability during maternal immune activation, which exposes the fetus to danger outside of the conceptus.