Pregnancy-associated plasma protein-A (PAPP-A) largest of the pregnancy associated proteins produced by both embryo and placenta ( syncytiocytotrophoblasts) during pregnancy (Placenta Notes). This protein is thought to have several different functions, including preventing recognition of the fetus by the maternal immune system, matrix mineralization and angiogenesis. Levels of PAPP-A rise from first detection in the first trimester until term.
Detection of this protein is also used as a first and second trimester diagnostic test for Trisomy 21. (More? Abnormal Development - Trisomy 21 - Down Syndrome)
Maternal serum concentrations are related to subsequent fetal growth and this relationship has suggested that it can be used as a diagnostic test for adverse pregnancy outcomes (intrauterine growth restriction, premature birth, preeclampsia, and stillbirth).
Alternative names: SP4, high molecular weight alpha-2 mobile pregnancy-specific protein, IGFBP4 protease
Page Links: Introduction | PAPP-A Levels | Some Recent Findings | Protein Structure | Coronary Disease | References | WWW Links | Glossary
Levels of PAPP-A rise from initial detection at about 32 days after ovulation, then increasing rapidly (levels doubling every 3 days), finally continuing to rise more slowly until term.
Electroimmunoassays allow the detection as early as the fifth week of pregnancy, of circulating levels down to 10 microgram/L.
Adult male serum PAPP-A circulating level is 8.03±2.75 mIU/L (mean±SD).
PAPP-A is a large zinc glycoprotein metalloproteinase and a member of the alpha-macroglobulin plasma protein family. It can bind cytokines and specifically cleave a binding protein for insulin-like growth factors (IGF binding protein 4 protease) therefore modulating cytokine activity. Metalloproteinases (or metalloproteases) are enzymes that specifically cleave proteins.
Protein is initially 1,627 amino acids in length and cleaved to 1,547 aa, with an N-terminal 22-amino acid signal peptide, followed by a highly basic arginine-rich propeptide of 58 amino acids.
Alternative names: SP4, high molecular weight alpha-2 mobile pregnancy-specific protein, IGFBP4 protease
Postnatally PAPP-A is also expressed in atherosclerotic plaques and circulating levels are elevated in acute coronary syndromes.
Kwik M, Morris J. Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome. Aust N Z J Obstet Gynaecol. 2003 Dec;43(6):438-42.
Tul N, Pusenjak S, Osredkar J, Spencer K, Novak-Antolic Z. Predicting complications of pregnancy with first-trimester maternal serum free-betahCG, PAPP-A and inhibin-A. Prenat Diagn. 2003 Dec 15;23(12):990-6.
Zhabin SG, Gorin VS, Judin NS. Review: immunomodulatory activity of pregnancy-associated plasma protein-A. J Clin Lab Immunol. 2003;52:41-50.
Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early-pregnancy origins of low birth weight. Nature. 2002 Jun 27;417(6892):916.
Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab. 2002 Apr;87(4):1762-7.
Search PubMed: term = Pregnancy-Associated Plasma Protein-A | PAPP-A |
1988 recommendations for neonates be assessed for follow-up care under the following conditions.
(see the NHMRC WWW Page)
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Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.
This current page is a link to Normal and Abnormal Development and Population Data.
Look at types of Abnormal Development that can occur during development.
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How do I find out if everything is OK with my developing baby and what are the tests that doctors carry out?
Prenatal diagnosis is based the various types of tests that can be carried out to inform parents and clinicians. With the rising age of mothers in Australia and new knowledge about family genetic history these tools are useful in helping clinicians check the developing fetus. Note that some tests, like ultrasound, are relatively non-invasive, informative, and carried out in many suburban clinics.
See also the Prenatal Diagnosis page NSW Pamphlet Checking your baby's health before birth.
Please email Dr Mark Hill if you wish to make a comment about this current project.