Mol. Hum. Reprod. Advance Access published online on September 18, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan054
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Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients
aDepartment of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan b21st Century COE Program, Development Center for Targeted and Minimally Invasive Diagnosis and Treatment cDivision of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan
Correspondence and request for reprint should be addressed to: Haruki Nishizawa, Department of Obstetrics and Gynecology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192 Japan, E-mail: nharuki{at}fujita-hu.ac.jp, Phone: +81-562-93-9294, Fax: +81-562-95-1821
Pregnancy-associated plasma protein-A and -A2 (PAPP-A and PAPP-A2) are proteases that cleave insulin-like growth factor binding proteins (IGFBPs), resulting in local activation of IGF signaling pathways. Here we examined PAPP-A and PAPP-A2 mRNA and protein levels in placenta and maternal sera from women with pre-eclampsia and compared them with samples from uncomplicated pregnancy. PAPP-A2 but not PAPP-A mRNA and protein were elevated in pre-eclamptic placenta (p<0.01). PAPP-A2 is normally produced in placental syncytiotrophoblast cells as well as maternal decidua. PAPP-A2 in syncytiotrophoblast cells was dramatically increased in pre-eclampsia. Maternal serum concentrations of PAPP-A2 but not PAPP-A were also significantly elevated in pre-eclampsia as compared to uncomplicated pregnancy. mRNA levels of IGFBP5, a specific substrate for PAPP-A2 protease activity, were also significantly increased, suggesting a potential role for IGFBP5 in fetal and placental growth suppression during pre-eclampsia. However, IGFBP5 protein levels were not increased in placenta from pre-eclampsia, possibly due to cleavage by upregulated PAPP-A2. These data might imply that PAPP-A2 may be upregulated in pre-eclamptic pregnancy in order to compensate for IGFBP5-mediated suppression of the IGF pathway, although final birth weights are still low in pre-eclamptic pregnancy.
Key Words: IGFBP5/PAPP-A/PAPP-A2/placenta/pre-eclampsia
* These authors contributed equally to this work.
Submitted on June 8, 2008; resubmitted on September 13, 2008; accepted on September 16, 2008.
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  J. Wang, Q. Qiu, M. Haider, M. Bell, A. Gruslin, and J. K Christians Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse J. Endocrinol., September 1, 2009; 202(3): 337 - 345. [Abstract] [Full Text] [PDF]
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