We predicted that, if the elevated expression of PAPP-A2 in preeclampsia in humans reflects a compensatory response, then deletion of Pappa2 in mice would exacerbate effects of Mmp9 deletion, i.e., mice null for both Pappa2 and Mmp9 would show a more severe phenotype than mice null for Mmp9 only. Here, PAPPA2 is linked to preeclampsia.