Levels of Alpha-Fetoprotein in Maternal Blood as a Screening Test for Fetal Neural-Tube Defect

Leighton, Pippa; Kitau, M. J.; Gordon, Y. B.; Leek, Angela; Chard, Tim

doi:10.1016/s0140-6736(75)90295-0

Cited by 64 publications

(20 citation statements)

References 20 publications

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“…3) when the conditions are adjusted for use of the assay with maternal sera. Similar sensitivity was found by Leighton et al (1975) and Vince et al (1975). More sensitive techniques with lower limits of detection of 0'1 to 1'5 p.gjl are more appropriate for normal human sera from the non-pregnant patient and have been described by Chayvialle and Ganguli (1973), Masseyeff et al (1974), Ruoslahti et al (1974), and Waldman et al (1973).…”

Section: Discussionsupporting

confidence: 52%

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An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol

1978

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SUMMARY A radioimmunoassay for cxl-fetoprotein in human maternal serum at 15-20 weeks' gestation using polyethylene glycol to separate bound and free antigen is described. A number of variables has been investigated to define optimal conditions for use at this gestation. The method gives results which agree with those from a double-antibody technique. It has good precision in the critical concentration range, and recoveries are satisfactory. The importance of including sufficient serum protein in the analytical system is stressed.There were systematic differences between three standard preparations of cxl-fetoprotein, but three out of four antisera tested gave very similar results. The implications for screening for neural tube defects in early pregnancy are discussed.

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Section: Discussionsupporting

confidence: 52%

“…Recent reports emphasise the value of maternal serum oo-fetoprotein (cxIF) measurements in the prenatal diagnosis of fetal neural tube defects (Leighton et al, 1975;Vince et al, 1975;UK Collaborative Study, 1977). Our own experience indicates the need for a simple, inexpensive, and properly characterised method to detect increases at 15 to 20 weeks' gestation.…”

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confidence: 99%

An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol

1978

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“…The protein produced by the embryo is transferred into the maternal blood circulation, and levels of AFP in the maternal serum are commonly used as a diagnostic marker to reveal developmental anomalies of the fetus [19,42,70]. Abnormally high levels of AFP in the maternal serum indicate an elevated risk of neural tube defects of the fetus such as spina bifida or anencephaly [54], whereas abnormally low levels indicates an elevated risk of Down's syndrome [22]. The synthesis of AFP decreases rapidly after birth and only trace amounts are detected in adults [3,83].…”

Section: Role Of A-fetoprotein In the Sexual Differentiation Of The Rmentioning

confidence: 99%

Role for estradiol in female-typical brain and behavioral sexual differentiation

Bakker

Baum

2008

Frontiers in Neuroendocrinology

170

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The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differentiation. Accordingly, it has been proposed that a-fetoprotein, a fetal plasma protein that binds estrogens with high affinity, has more than a neuroprotective role and specifically delivers estrogens to target brain cells to ensure female differentiation. Here, we review new results obtained in aromatase and a-fetoprotein knockout mice showing that estrogens can have both feminizing and defeminizing effects on the developing neural mechanisms that control sexual behavior. We propose that the defeminizing action of estradiol normally occurs prenatally in males and is avoided in fetal females because of the protective actions of a-fetoprotein, whereas the feminizing action of estradiol normally occurs postnatally in genetic females.

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“…The protein expressed by the embryo is transferred to the maternal blood circulation, and abnormal levels of embryonic AFP in the maternal serum are indicative of spina bifida or Down's syndrome in the fetus (3,4). The synthesis of AFP decreases dramatically after birth, and only trace amounts are detected in the adult (2).…”

mentioning

confidence: 99%

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

Gabant

Forrester

Nichols

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The alpha-fetoprotein gene (Afp) is a member of a multigenic family that comprises the related genes encoding albumin, alphaalbumin, and vitamin D binding protein. The biological role of this major embryonic serum protein is unknown although numerous speculations have been made. We have used gene targeting to show that AFP is not required for embryonic development. AFP null embryos develop normally, and individually transplanted homozygous embryos can develop in an AFP-deficient microenvironment. Whereas mutant homozygous adult males are viable and fertile, AFP null females are infertile. Our analyses of these mice indicate that the defect is caused by a dysfunction of the hypothalamic͞ pituitary system, leading to anovulation.A lpha-fetoprotein (AFP) is a serum glycoprotein produced at high levels during fetal life by the liver and the visceral endoderm of the yolk sac and at lower levels by the developing gastrointestinal tract (1, 2). The protein expressed by the embryo is transferred to the maternal blood circulation, and abnormal levels of embryonic AFP in the maternal serum are indicative of spina bifida or Down's syndrome in the fetus (3, 4). The synthesis of AFP decreases dramatically after birth, and only trace amounts are detected in the adult (2). AFP expression has been shown to be regulated by transcriptional mechanisms involving a relatively large promoter (P1) and three distant enhancers (for reviews see refs. 5 and 6). More recently it has been shown that the first intron of the Afp gene contains an enhancer and an alternative promoter called P2 (7). The genes of the albumin family are linked in the mammalian genomes, and this conserved organization has been proposed to be important for the developmental expression switch of the genes of the family after birth (8). Several hypotheses have been proposed for the physiological function of AFP (for reviews see refs. 6, 9, and 10). Because AFP is synthesized during the cell cycle G 1 and S phases, it has been hypothesized that it affects cell growth (11, 12). The observation that AFP is able to bind estrogen led to the suggestion that AFP plays a role in sexual differentiation of the brain by protecting the fetus from the effects of circulating estrogen (13). In addition to binding estrogen, AFP, like albumin, is able to bind other steroids as well as endogenous and exogenous substances such as fatty acids, bilirubin, and various pharmaceutical agents, suggesting that AFP may play a general transportation role (for review see ref. 14). Moreover, because cellular internalization of the protein has been reported, AFP could also interact with cytoplasmic chaperone proteins that normally escort nuclear receptors or transcription cofactors through the cytoplasm toward organelle interfaces (15, 16). AFP has also been proposed to be one protein that protects the embryo against the maternal immune system, on the basis of the observation that addition of purified AFP into the culture of splenic or lymph node mononuclear cells exerts a suppressive effect on ant...

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Levels of Alpha-Fetoprotein in Maternal Blood as a Screening Test for Fetal Neural-Tube Defect

Cited by 64 publications

References 20 publications

An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol

An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol

Role for estradiol in female-typical brain and behavioral sexual differentiation

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

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Levels of Alpha-Fetoprotein in Maternal Blood as a Screening Test for Fetal Neural-Tube Defect

Cited by 64 publications

References 20 publications

An Optimised Radioimmunoassay for mAternal Serum α1-Fetoprotein using Polyethylene Glycol

An Optimised Radioimmunoassay for mAternal Serum α1-Fetoprotein using Polyethylene Glycol

Role for estradiol in female-typical brain and behavioral sexual differentiation

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

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Product

Resources

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An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol

An Optimised Radioimmunoassay for mAternal Serum α₁-Fetoprotein using Polyethylene Glycol