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Mol. Hum. Reprod. Advance Access originally published online on September 18, 2008
Molecular Human Reproduction 2008 14(10):595-602; doi:10.1093/molehr/gan054
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients

Haruki Nishizawa1,2,4,{dagger}, Kanako Pryor-Koishi1,2,{dagger}, Machiko Suzuki1,2, Takema Kato2,3, Hiroshi Kogo3, Takao Sekiya1, Hiroki Kurahashi2,3 and Yasuhiro Udagawa1

1Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan 221st Century COE Program, Development Center for Targeted and Minimally Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Japan 3Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan

4 Correspondence address. Tel: +81-562-93-9294; Fax: +81-562-95-1821; E-mail: nharuki{at}fujita-hu.ac.jp

Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -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 -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 and 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 with 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 up-regulated PAPP-A2. These data might imply that PAPP-A2 may be up-regulated in pre-eclamptic pregnancy to compensate for IGFBP5-mediated suppression of the IGF pathway, although final birthweights are still low in pre-eclamptic pregnancy.

Key words: IGFBP5/PAPP-A/PAPP-A2/placenta/pre-eclampsia

{dagger} 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
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[Abstract] [Full Text] [PDF]


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