dr. Julian christians

Simon Fraser University

SSB8101 - 8888 University Drive

Burnaby, BC V5A 1S6

Placental Development

Pre-eclampsia

The placenta is responsible for the transfer of nutrients and oxygen from a pregnant woman to her fetus.  The proper development of the placenta is therefore critical for the health of the fetus, as well as for the well-being of the mother.  Currently, only a few biomarkers of placental dysfunction are available for early diagnosis of complications.  Pregnancy-associated plasma protein A (PAPPA) is one such marker.  This protein is produced at high levels in human placenta and is secreted into the blood of the mother.  Lower than normal PAPPA levels in the circulation of pregnant women are associated with higher risk of preterm delivery, low birth weight, pregnancy loss and preeclampsia.  The diagnostic power of current markers such as PAPPA is limited, and further markers are needed.  Recently, a novel protein structurally related to PAPPA was discovered and named PAPPA2.  PAPPA2 is also expressed at high levels in the placenta but its physiological functions remain unknown.  However, our previous work has provided some evidence that PAPPA2 is associated with variation in growth in mice.  We are currently investigating the physiological roles of PAPPA2 in the placenta, using a mouse model. The proposed work will determine the role of PAPPA2 in placental development, and assess whether there is justification for studying association between circulating PAPPA2 levels and pregnancy outcomes in humans.  If so, this protein will be useful as a biomarker of placental dysfunction, which could enable earlier and more accurate diagnoses and, therefore, more effective treatments.

Christians, J.K., Hoeflich, A. and Keightley, P.D. (2006) PAPPA2, an enzyme that cleaves an insulin-like growth factor binding protein, is a candidate gene for a QTL affecting body size in mice.  Genetics 173: 1547–1553.