Placental defects in α7 integrin null mice

The alpha 7 beta 1 integrin is a heterodimeric transmembrane receptor that links laminin in the extracellular matrix to the cell cytoskeleton. Loss of the alpha 7 integrin chain results in partial embryonic lethality. We have previously shown that alpha 7 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 alpha 7 integrin null embryos may contribute to the partial embryonic lethality. Placentae from embryonic day (ED) 9.5 and 13.5 alpha 7 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 alpha 7 integrin weighed less compared to wild-type controls. Blood vessels within the placental labyrinth of alpha 7 integrin null embryos exhibited fewer differentiated vascular smooth muscle cells compared to wild-type. Loss of the alpha 7 integrin resulted in altered extracellular matrix deposition and reduced expression of alpha 5 integrin. Together our results confirm a role for the alpha 7 beta 1 integrin in placental vascular development and demonstrate for the first time that loss of the alpha 7 integrin results in placental defects. (c) 2007 Elsevier Ltd. All rights reserved.