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This Article Accepted manuscript (PDF) Supplementary figure 1 All Versions of this Article: JOE-09-0136v1 202/3/337    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, J. Articles by Christians, J. PubMed PubMed Citation Articles by Wang, J. Articles by Christians, J.

J Wang, Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
Q Qiu, Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
M Haider, Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
M Bell, Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
A Gruslin, Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
J Christians, Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada

Correspondence: Julian Christians, Email: julian_christians{at}sfu.ca

Pregnancy-associated plasma protein-A and -A2 (PAPPA and PAPPA2) are proteases that cleave insulin-like growth factor-binding proteins (IGFBPs) and thereby increase the bioavailability of growth factors. PAPPA has long been recognized as a marker of fetal genetic disorders and adverse pregnancy outcomes. In contrast, although PAPPA2 is also highly expressed in human placenta, its physiological importance is not clear. To establish whether mice will be a useful model for the study of PAPPA2, we compared the patterns of expression of PAPPA2 in the placentae of mouse and human. We show for the first time that PAPPA2 is highly expressed in mouse placenta, as is the case in humans. Specifically, it is expressed at the interface of the maternal and fetal layers of the mouse placenta at all gestational stages studied (10.5 – 16.5 dpc). Similarly, PAPPA2 is expressed in the syncytiotrophoblast layer of human placental villi and is also detected in some invasive extravillous trophoblasts in the first trimester. These results are consistent with a model whereby PAPPA2 cleaves IGFBPs produced in the maternal decidua to promote feto-placental growth, and indicate that this protein may play analogous roles in human and mouse placenta. PAPPA2 protein is detectable in the circulation of pregnant mice and humans during the first trimester and at term, raising the possibility that PAPPA2 may be a useful biomarker of placental dysfunction. PAPPA2 also shows specific localization within the mouse embryo and therefore may play roles in fetal development, independent of its action in the placenta.