Alpha-Fetoprotein

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Introduction

The alpha-fetoprotein (AFP) or fetal alpha globulin is thought to function in the fetus in a similar role to that of serum albumin postnatally. AFP is synthesised in both the fetal liver and the yolk sac.

The AFP test is a test that is performed during pregnancy of maternal blood or fetal amniotic fluid at 16-19 weeks of gestation. The amniotic test (Amniocentesis) is more invasive than the maternal blood test. The protein is synthesized by yolk sac and liver of the fetus and is also expressed in the adult in some liver cancers and is a member of a multigenic family encoding albumin, alpha-albumin, and vitamin D binding protein.

Low levels of AFP normally occur in the blood of a pregnant woman. Abnormal amounts of the protein may indicate genetic or developmental problems in the fetus. High levels may indicate neural tube defects (spina bifida, anencephaly), the neural tube defect allows AFP to leak through into the amniotic fluid. This test can also be used in non-pregnacy testing of clinical conditions, including liver cancer.


Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

Some Recent Findings

Trisomy 21 newborn
  • Second Trimester Prenatal Screening for Down's Syndrome (DS) in Mainland Chinese Subjects using Double-Marker Analysis of α-fetoprotein and β-human Chorionic Gonadotropin Combined with Measurement of Nuchal Fold Thickness ( NT)[1] "Second trimester prenatal screening using double-marker analysis for AFP and β-hCG combined with measurement of NT is effective for the detection of DS in Mainland Chinese pregnancies."
More recent papers  
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Search term: Alpha-Fetoprotein

Aruna R Patil, Shrivalli Nandikoor, Govindarajan Mallarajapatna, Swarna Shivakumar Case 248: Cystic Duodenal Dystrophy with Groove Pancreatitis. Radiology: 2017, 285(3);1045-1051 PubMed 29155635

Yasen Aimaiti, Xin Jin, Wei Wang, Zixin Chen, Dewei Li TGF-β1 signaling regulates mouse hepatic stellate cell differentiation via the Jagged1/Notch pathway. Life Sci.: 2017; PubMed 29154784

Chao He, Xiaoyun Zhang, Chuan Li, Wei Peng, Tian-Fu Wen, Lv-Nan Yan, Jiayin Yang, Wusheng Lu Changes of alpha-fetoprotein levels could predict recurrent hepatocellular carcinoma survival after trans-arterial chemoembolization. Oncotarget: 2017, 8(49);85599-85611 PubMed 29156744

Protein

  • Protein first identified in the 1950's.[2]
  • AFP Levels - normal values for males or non-pregnant females is less than 10 micrograms/millilitre.
  • Member of the albuminoid gene superfamily which includes, serum albumin, vitamin D binding protein and alpha-albumin (afamin).[3]
  • Screening has low sensitivity for fetal hydrocephalus and is rarely elevated in isolated cases.[4]
    • When fetal hydrocephalus is detected, elevated AFP levels indicate that the fetus is at significant risk to have additional malformations.
  • Serum alpha fetoprotein (AFP) has also been used as a tumor marker in the adult for liver cancer (Hepatocellular carcinoma, HCC).[5]
  • Stem cell researchers have used AFP expression as an early marker to identify differentiation of endoderm germ layer in embryoid bodies.[6]

Female Function

  • In knockout KO Mice, essential for female fertility and for expression of normal female behaviors.[7]
    • sequestrates estrogens
    • protects the female developing brain from deleterious (defeminizing/masculinizing) effects of these hormones.[8]
    • mice suffer from anovulation

Postnatal Diagnostic Uses

  • Serum α-fetoprotein (AFP) level is used as a tumour marker for the diagnosis and detection of hepatocellular carcinoma.
    • elevated AFP level (≥ 200 ng/dL)
  • Some patients have hereditary persistence of AFP and also have persistent abnormal AFP.

Protein Sequence

Length 609 Mass (Da) 68,678

>sp|P02771|FETA_HUMAN Alpha-fetoprotein OS=Homo sapiens GN=AFP PE=1 SV=1 MKWVESIFLIFLLNFTESRTLHRNEYGIASILDSYQCTAEISLADLATIFFAQFVQEATY KEVSKMVKDALTAIEKPTGDEQSSGCLENQLPAFLEELCHEKEILEKYGHSDCCSQSEEG RHNCFLAHKKPTPASIPLFQVPEPVTSCEAYEEDRETFMNKFIYEIARRHPFLYAPTILL WAARYDKIIPSCCKAENAVECFQTKAATVTKELRESSLLNQHACAVMKNFGTRTFQAITV TKLSQKFTKVNFTEIQKLVLDVAHVHEHCCRGDVLDCLQDGEKIMSYICSQQDTLSNKIT ECCKLTTLERGQCIIHAENDEKPEGLSPNLNRFLGDRDFNQFSSGEKNIFLASFVHEYSR RHPQLAVSVILRVAKGYQELLEKCFQTENPLECQDKGEEELQKYIQESQALAKRSCGLFQ KLGEYYLQNAFLVAYTKKAPQLTSSELMAITRKMAATAATCCQLSEDKLLACGEGAADII IGHLCIRHEMTPVNPGVGQCCTSSYANRRPCFSSLVVDETYVPPAFSDDKFIFHKDLCQA QGVALQTMKQEFLINLVKQKPQITEEQLEAVIADFSGLLEKCCQGQEQEVCFAEEGQKLI SKTRAALGV

Human Albuminoid Family

Other than AFP, all albuminoid family genes are located on chromosome 4 and the proteins are synthesised in the adult liver.

  1. Alpha-fetoprotein (Mr 69K)
  2. Serum albumin (Mr 66K)
  3. Alpha-albumin (Mr 82K)
  4. Vitamin-D-binding protein (Mr 58K)

References

  1. Fang Liu, Hongyan Liang, Xiaofeng Jiang, Yu Zhang, Li Xue, Chun Yang, Jing Cheng, Peijia Liu, Yang Liu, Xiaoying Guo Second trimester prenatal screening for Down's syndrome in Mainland Chinese subjects using double-marker analysis of α-fetoprotein and β-human chorionic gonadotropin combined with measurement of nuchal fold thickness. Ann. Acad. Med. Singap.: 2011, 40(7);315-8 PubMed 21870022
  2. C G BERGSTRAND, B CZAR Demonstration of a new protein fraction in serum from the human fetus. Scand. J. Clin. Lab. Invest.: 1956, 8(2);174 PubMed 13351554
  3. Gerald J Mizejewski Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp. Biol. Med. (Maywood): 2004, 229(6);439-63 PubMed 15169963
  4. Maternal serum alpha-fetoprotein levels in fetal hydrocephalus: a retrospective population based study. Terrence P Szajkowski, Bernard N Chodirker, Karen M MacDonald, and Jane A Evans BMC Pregnancy Childbirth. 2006; 6: 23. Published online 2006 July 7. doi: 10.1186/1471-2393-6-23. PMCID: PMC1526755
  5. Gerald J Mizejewski Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp. Biol. Med. (Maywood): 2004, 229(6);439-63 PubMed 15169963
  6. Mari Pekkanen-Mattila, Markku Pelto-Huikko, Ville Kujala, Riitta Suuronen, Heli Skottman, Katriina Aalto-Setälä, Erja Kerkelä Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem. Cell Biol.: 2010, 133(5);595-606 PubMed 20369364
  7. Christelle De Mees, Julie Bakker, Josiane Szpirer, Claude Szpirer Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility. Biomark Insights: 2007, 1;82-5 PubMed 19690639
  8. Julie Bakker, Christelle De Mees, Quentin Douhard, Jacques Balthazart, Philippe Gabant, Josiane Szpirer, Claude Szpirer Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nat. Neurosci.: 2006, 9(2);220-6 PubMed 16388309

Reviews

Gerald J Mizejewski Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family. Tumour Biol.: 2011, 32(2);241-58 PubMed 21120646

A C Houwert, J C Giltay, E G W M Lentjes, M T W T Lock Hereditary persistence of alpha-fetoprotein (HPAF P): review of the literature. Neth J Med: 2010, 68(11);354-8 PubMed 21116028

Wei Yuan, Lina Chen, Andrés López Bernal Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk? A systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol.: 2009, 145(1);57-64 PubMed 19457604

A A Terentiev, N T Moldogazieva Structural and functional mapping of alpha-fetoprotein. Biochemistry Mosc.: 2006, 71(2);120-32 PubMed 16489915

G J Mizejewski Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp. Biol. Med. (Maywood): 2001, 226(5);377-408 PubMed 11393167


Articles

Sonia L La'ulu, Kyle J Rasmussen, William L Roberts Pediatric reference intervals for serum alpha-fetoprotein. Clin. Chim. Acta: 2011, 412(17-18);1695-6 PubMed 21640088

M J Murray, J C Nicholson α-Fetoprotein. Arch Dis Child Educ Pract Ed: 2011, 96(4);141-7 PubMed 21613305


Search PubMed

Search PubMed: Alpha-Fetoprotein



Prenatal Diagnosis Terms

  • ART - Assisted Reproductive Technology a general term to describe all the clinical techniques used to aid fertility.
  • blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
  • blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
  • cell-free fetal deoxyribonucleic acid - (cffDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood.
  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
  • polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • pre-implantation genetic diagnosis - (PGD, pre-implantation genetic screening) a diagnostic procedure for embryos produced through Assisted Reproductive Technology (ART, in vitro fertilisation, IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
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Cite this page: Hill, M.A. 2017 Embryology Alpha-Fetoprotein. Retrieved November 22, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Alpha-Fetoprotein

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