Christians Lab
PAPP-A2 in pregnancy
PAPP-A2 is one of the most consistently upregulated genes in preeclampsia. However, it is not known whether PAPP-A2 upregulation impairs placental development, causing pregnancy complications, or whether its upregulation is a compensatory response to placental pathology. We showed that PAPP-A2 is highly expressed in homologous regions of mouse and human placentae, and identified factors that might cause the upregulation of PAPP-A2 (Wang et al 2009; Wagner et al. 2011). We found that PAPP-A2 and its downstream target, IGFBP-5, were present in the placenta very early in pregnancy and affected the behaviour of placental cells (Crosley et al 2014a). Furthermore, PAPP-A2 levels were elevated in the first-trimester maternal circulation in pregnancies that subsequently developed preeclampsia (Crosley et al 2014b), a finding since confirmed by others. To test the hypothesis that PAPP-A2 is upregulated as a compensatory response to placental pathology, we deleted PAPP-A2 in a mouse model of impaired placental development. The absence of PAPP-A2 did not exacerbate the model, suggesting that PAPP-A2 is not required for compensation (Christians et al 2018). Understanding the mechanisms underlying the association between PAPP-A2 and disease will improve screening strategies to allow earlier identification of at-risk pregnancies, as well as the development of therapeutic interventions.Relevant papers
Christians JK, Lennie KI, Huicochea Munoz MF, Binning N (2018) PAPP-A2 deficiency does not exacerbate the phenotype of a mouse model of intrauterine growth restriction. Reprod Biol Endocrinol 16:58.Crosley EJ, Dunk CE, Beristain AG, Christians JK (2014a) IGFBP-4 and -5 are expressed in first-trimester villi and differentially regulate the migration of HTR-8/SVneo cells. Reprod Biol Endocrinol 12: 123.
Crosley EJ, Durland U, Seethram K, Macrae S, Gruslin A, Christians JK. (2014b) First-trimester levels of pregnancy-associated plasma protein A2 (PAPP-A2) in the maternal circulation are elevated in pregnancies that subsequently develop preeclampsia. Reprod Sci 21: 754–60.
Wagner PK, Otomo A, Christians JK (2011) Regulation of pregnancy-associated plasma protein A2 (PAPPA2) in a human placental trophoblast cell line (BeWo). Reprod Biol Endocrinol 9: 48.
Wang J, Qiu Q, Haider M, Bell M, Gruslin A, Christians JK (2009) Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse. J Endocrinol 202: 337-345.