Project description:The alpha-fetoprotein (AFP) gene is a member of the albumin gene family and encodes a serum glycoprotein with an onco-fetal pattern of expression. AFP is produced in high concentrations during embryonic life by the hepatocytes and the visceral endoderm of the yolk sac and to a lesser extent by the developing gastrointestinal tract and kidney. Alpha-fetoprotein is the major serum fetal protein in mammals, with a concentration that reaches the order of several mg/ml. Its synthesis decreases dramatically shortly after birth to reach only trace amounts a few weeks later but can be restored during life when liver pathologies or some types of tumors develop (hepatitis, cirrhosis, hepatoma, teratocarcinoma, and some pancreatic and renal tumors). AFP is then mainly expressed by the adult liver. AFP produced by the embryo is secreted in the amniotic fluid and is able to cross the placental barrier to reach the maternal blood circulation, where its titer is used as a diagnostic marker to reveal developmental anomalies of the fetus. Abnormally high levels of AFP in the maternal serum indicates elevated risk for neural tube defects of the fetus such as spina bifida or anencephaly, whereas abnormally low levels indicates elevated risk for a Down’s syndrome. Measurements of the AFP levels in the maternal serum are undertaken at 14-22 weeks of each pregnancy and are part, along with unconjugated estradiol, human chorionic gonadotropin and inhibin A, of the quadruple test for antenatal Down’s syndrome screening. Abnormal AFP levels can also be indicative of other fetal pathologies. The reason why these pathologies induce abnormal levels of AFP is still not known. Homozygous Afp knock-out females (AFP KO) are sterile, due to anovulation. Ovaries contain mature follicles and are functional, but lack a proper signal from the hypothalamic-pituitarian axis (HPG) in order to ovulate. The expression profile of several genes in the HPG is impaired. Furthermore, AFP KO females are masculinized and defeminized. They exhibit a loss of female sexual behaviour (no lordosis) and a male pattern of tyrosine hydroxylase expressing neurons distribution in some sexual dimorphic areas of the brain. The phenotype of those mice is a consequence of an estrogen overexposure of their brains during the perinatal period. This phenotype can be reversed if these mice develop in an embryonic environment strongly reduced in estrogens. Homozygous AFP KO mice that developed in those conditions are fertile in adulthood (no further treatment needed), and exhibit proper sexual behaviour. cDNA microarray analysis of embryonic and adult liver tissue of AFP1 kO mice. Single mutant mice were analysed versus a pool of wt RNA in two technical replicates (only for adult tissue) including a dye swap experiment. In total 6 adult mutant male mice and 6 embryos (3 male and 3 female) were analysed

Project description:The alpha-fetoprotein (AFP) gene is a member of the albumin gene family and encodes a serum glycoprotein with an onco-fetal pattern of expression. AFP is produced in high concentrations during embryonic life by the hepatocytes and the visceral endoderm of the yolk sac and to a lesser extent by the developing gastrointestinal tract and kidney. Alpha-fetoprotein is the major serum fetal protein in mammals, with a concentration that reaches the order of several mg/ml. Its synthesis decreases dramatically shortly after birth to reach only trace amounts a few weeks later but can be restored during life when liver pathologies or some types of tumors develop (hepatitis, cirrhosis, hepatoma, teratocarcinoma, and some pancreatic and renal tumors). AFP is then mainly expressed by the adult liver. AFP produced by the embryo is secreted in the amniotic fluid and is able to cross the placental barrier to reach the maternal blood circulation, where its titer is used as a diagnostic marker to reveal developmental anomalies of the fetus. Abnormally high levels of AFP in the maternal serum indicates elevated risk for neural tube defects of the fetus such as spina bifida or anencephaly, whereas abnormally low levels indicates elevated risk for a Down’s syndrome. Measurements of the AFP levels in the maternal serum are undertaken at 14-22 weeks of each pregnancy and are part, along with unconjugated estradiol, human chorionic gonadotropin and inhibin A, of the quadruple test for antenatal Down’s syndrome screening. Abnormal AFP levels can also be indicative of other fetal pathologies. The reason why these pathologies induce abnormal levels of AFP is still not known. Homozygous Afp knock-out females (AFP KO) are sterile, due to anovulation. Ovaries contain mature follicles and are functional, but lack a proper signal from the hypothalamic-pituitarian axis (HPG) in order to ovulate. The expression profile of several genes in the HPG is impaired. Furthermore, AFP KO females are masculinized and defeminized. They exhibit a loss of female sexual behaviour (no lordosis) and a male pattern of tyrosine hydroxylase expressing neurons distribution in some sexual dimorphic areas of the brain. The phenotype of those mice is a consequence of an estrogen overexposure of their brains during the perinatal period. This phenotype can be reversed if these mice develop in an embryonic environment strongly reduced in estrogens. Homozygous AFP KO mice that developed in those conditions are fertile in adulthood (no further treatment needed), and exhibit proper sexual behaviour.

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Up-regulated aldo-ketoreductase1B10 in chronic hepatitis C: Association with serum alpha-fetoprotein and hepatocellular carcinoma

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