title: SNAT2 expression and regulation in human growth-restricted placentas.
abstract: BACKGROUND
  Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies.
  
  
  METHODS
  We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination.
  
  
  RESULTS
  mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups.
  
  
  CONCLUSIONS
  This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mandò
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.forename: Paola
authors.initials: P
authors.lastname: Pileri
authors.forename: Patrizia
authors.initials: P
authors.lastname: Colapietro
authors.forename: Maria Antonella
authors.initials: MA
authors.lastname: Marino
authors.forename: Laura
authors.initials: L
authors.lastname: Avagliano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Doi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bulfamante
authors.forename: Monica
authors.initials: M
authors.lastname: Miozzo
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
mesh_terms: D000328:Adult; D026924:Amino Acid Transport System A / Q000378:metabolism*; D002585:Cesarean Section; D019175:DNA Methylation / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005787:Gene Frequency; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D012039:Regional Blood Flow / Q000502:physiology; D017422:Sequence Analysis, DNA
chemical_list: D026924:Amino Acid Transport System A; D017931:DNA Primers; C498797:SLC38A2 protein, human