Pregnancy-associated plasma protein A2 (PAPPA2) expression in the placenta

Pregnancy-associated plasma protein A2 (PAPPA2), an insulin-like growth factor binding protein-5 (IGFBP-5) protease, has been shown to be upregulated during pre-eclampsia, a serious hypertensive disorder that occurs during pregnancy. The goal of this thesis was to study placental PAPPA2 expression using mice and cell culture models. In mice with natural genetic variation at the PAPPA2 gene, there was large variation in placental PAPPA2 expression, but this did not alter pregnancy outcomes, such as birth weight. In order to study potential factors regulating PAPPA2 expression, the human choriocarcinoma cell line, BeWo, was used as a model of placental trophoblasts. Hypoxia, prostaglandin E2, and tumor necrosis factor-alpha (factors present at elevated levels in pre-eclampsia) all caused PAPPA2 upregulation. Both the mouse and cell culture results are consistent with the hypothesis that PAPPA2 is upregulated in response to placental pathology, rather than being a cause of pregnancy complications.