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Background  Pregnancy-associated plasma protein-A2 (PAPP-A2) is consistently upregulated in the placentae of pregnancies complicated by preeclampsia and fetal growth restriction. The causes and significance of this upregulation remain unknown, but it has been hypothesized that it is a compensatory response to improve placental growth and development. We predicted that, if the upregulation of PAPP-A2 in pregnancy complications reflects a compensatory response, then deletion of  Pappa2  in mice would exacerbate the effects of a gene deletion previously reported to impair placental development: deficiency of matrix metalloproteinase-9 (MMP9).    Methods  We crossed mice carrying deletions in  Pappa2  and  Mmp9  to produce pregnancies deficient in one, both, or neither of these genes. We measured pregnancy rates, number of conceptuses, fetal and placental growth, and the histological structure of the placenta.    Results  We found no evidence of reduced fertility, increased pregnancy loss, or increased fetal demise in  Mmp9   −/−   females. In pregnancies segregating for  Mmp9 ,  Mmp9   −/−   fetuses were lighter than their siblings with a functional  Mmp9  allele. However, deletion of  Pappa2  did not exacerbate or reveal any effects of  Mmp9  deficiency. We observed some effects of  Pappa2  deletion on placental structure that were independent of  Mmp9  deficiency, but no effects on fetal growth. At G16, male fetuses were heavier than female fetuses and had heavier placentae with larger junctional zones and smaller labyrinths.    Conclusions  Effects of  Mmp9  deficiency were not exacerbated by the deletion of  Pappa2 . Our results do not provide evidence that upregulation of placental PAPP-A2 represents a mechanism to compensate for impaired fetal growth.    Electronic supplementary material  The online version of this article (10.1186/s12958-018-0376-4) contains supplementary material, which is available to authorized users.

PAPP-A2 deficiency does not exacerbate the phenotype of a mouse model of intrauterine growth restriction