Placental Defects in α7 Integrin Null Mice

Abstract

The α7β1 integrin is a heterodimeric transmembrane receptor that links laminin in the extracellular matrix to the cell cytoskeleton. Loss of the α7 integrin chain results in partial embryonic lethality. We have previously shown that α7 integrin null embryos exhibit vascular smooth muscle cell defects that result in cerebral vascular hemorrhaging. Since the placenta is highly vascularized, we hypothesized that placental vascular defects in α7 integrin null embryos may contribute to the partial embryonic lethality. Placentae from embryonic day (ED) 9.5 and 13.5 α7 integrin knockout embryos showed structural defects including infiltration of the spongiotrophoblast layer into the placental labyrinth, a reduction in the placental labyrinth and loss of distinct placental layers. Embryos and placentae that lacked the α7 integrin weighed less compared to wild-type controls. Blood vessels within the placental labyrinth of α7 integrin null embryos exhibited fewer differentiated vascular smooth muscle cells compared to wild-type. Loss of the α7 integrin resulted in altered extracellular matrix deposition and reduced expression of α5 integrin. Together our results confirm a role for the α7β1 integrin in placental vascular development and demonstrate for the first time that loss of the α7 integrin results in placental defects.