|Embryology - 27 Feb 2020 Expand to Translate|
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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. May also be an indicator of embryo ventral wall defects and abnormal placental structure. This test can also be used in non-pregnacy testing of clinical conditions, including liver disease.
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.|
- Protein first identified in the 1950's.
- 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).
- Screening has low sensitivity for fetal hydrocephalus and is rarely elevated in isolated cases.
- 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).
- Stem cell researchers have used AFP expression as an early marker to identify differentiation of endoderm germ layer in embryoid bodies.
- In knockout KO Mice, essential for female fertility and for expression of normal female behaviors.
- sequestrates estrogens
- protects the female developing brain from deleterious (defeminizing/masculinizing) effects of these hormones.
- mice suffer from anovulation
Alpha-fetoprotein combined with other markers was part of a second trimester serum screening for Trisomy 21 syndrome.
- triple test - (alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and unconjugated estriol)
- quadruple test - (alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG), unconjugated estriol), and inhibin A.
- Links: Trisomy 21
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.
- See Clinical Trial
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.
- Alpha-fetoprotein (Mr 69K)
- Serum albumin (Mr 66K)
- Alpha-albumin (Mr 82K)
- Vitamin-D-binding protein (Mr 58K)
- Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP, Nelson SM, Cameron AD, Connor MJ & Dobbie R. (2006). Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol , 107, 161-6. PMID: 16394054 DOI.
- Sultana C, Diţă C, Botescu A, Grancea C & Ruţă S. (2014). SERUM ALPHA FETOPROTEIN, A SURROGATE MARKER FOR LIVER DISEASE PROGRESSION IN CHRONIC HEPATITIS C. Roum Arch Microbiol Immunol , 73, 69-73. PMID: 26201121
- Hughes AE, Sovio U, Gaccioli F, Cook E, Charnock-Jones DS & Smith GCS. (2019). The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome. Placenta , 81, 25-31. PMID: 31138428 DOI.
- Dinglas C, Afsar N, Cochrane E, Davis J, Kim S, Akerman M, Wells M, Chavez M, Herrera K, Heo H & Vintzileos A. (2019). First trimester maternal serum alpha fetoprotein is associated with ischemic placental disease. Am. J. Obstet. Gynecol. , , . PMID: 31794723 DOI.
- Liu F, Liang H, Jiang X, Zhang Y, Xue L, Yang C, Cheng J, Liu P, Liu Y & Guo X. (2011). 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. , 40, 315-8. PMID: 21870022
- BERGSTRAND CG & CZAR B. (1956). Demonstration of a new protein fraction in serum from the human fetus. Scand. J. Clin. Lab. Invest. , 8, 174. PMID: 13351554 DOI.
- Mizejewski GJ. (2004). Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp. Biol. Med. (Maywood) , 229, 439-63. PMID: 15169963
- 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
- Pekkanen-Mattila M, Pelto-Huikko M, Kujala V, Suuronen R, Skottman H, Aalto-Setälä K & Kerkelä E. (2010). Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem. Cell Biol. , 133, 595-606. PMID: 20369364 DOI.
- De Mees C, Bakker J, Szpirer J & Szpirer C. (2007). Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility. Biomark Insights , 1, 82-5. PMID: 19690639
- Bakker J, De Mees C, Douhard Q, Balthazart J, Gabant P, Szpirer J & Szpirer C. (2006). Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nat. Neurosci. , 9, 220-6. PMID: 16388309 DOI.
- Morris RK, Cnossen JS, Langejans M, Robson SC, Kleijnen J, Ter Riet G, Mol BW, van der Post JA & Khan KS. (2008). Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: systematic review and meta-analysis. BMC Pregnancy Childbirth , 8, 33. PMID: 18680570 DOI.
Houwert AC, Giltay JC, Lentjes EG & Lock MT. (2010). Hereditary persistence of alpha-fetoprotein (HPAF P): review of the literature. Neth J Med , 68, 354-8. PMID: 21116028
Yuan W, Chen L & Bernal AL. (2009). 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. , 145, 57-64. PMID: 19457604 DOI.
Terentiev AA & Moldogazieva NT. (2006). Structural and functional mapping of alpha-fetoprotein. Biochemistry Mosc. , 71, 120-32. PMID: 16489915
Mizejewski GJ. (2001). Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp. Biol. Med. (Maywood) , 226, 377-408. PMID: 11393167
De Mees C, Bakker J, Szpirer J & Szpirer C. (2007). Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility. Biomark Insights , 1, 82-5. PMID: 19690639
Ball D, Rose E & Alpert E. (1992). Alpha-fetoprotein levels in normal adults. Am. J. Med. Sci. , 303, 157-9. PMID: 1375809
Search PubMed: Alpha-Fetoprotein
- 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 - (cfDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood. Can be performed from GA 10 weeks as a first-tier test or as a second-tier test, with women with increased probability on combined first trimester screening offered cfDNA or diagnostic testing.
- 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.
- free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.
- multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.
- 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.
- quadruple test (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, unconjugated estriol, and inhibin A) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
- single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
- triple test - (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, and unconjugated estriol) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
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Cite this page: Hill, M.A. (2020, February 27) Embryology Alpha-Fetoprotein. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Alpha-Fetoprotein
- © Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G