title: Amniotic fluid and serum biomarkers from women with neural tube defect-affected pregnancies: a case study for myelomeningocele and anencephaly: clinical article.
abstract: OBJECTIVE
  The authors sought to identify novel biomarkers for early detection of neural tube defects (NTDs) in human fetuses.
  
  
  METHODS
  Amniotic fluid and serum were drawn from women in the second trimester of pregnancy. The study group included 2 women pregnant with normal fetuses and 4 with fetuses displaying myelomeningocele (n = 1), anencephaly (n = 1), holoprosencephaly (n = 1), or encephalocele (n = 1). Amniotic fluid stem cells (AFSCs) were isolated and cultured. The cells were immunostained for the stem cell markers Oct4, CD133, and Sox2; the epigenetic biomarkers H3K4me2, H3K4me3, H3K27me2, H3K27me3, H3K9Ac, and H3K18Ac; and the histone modifiers KDM6B (a histone H3K27 demethylase) and Gcn5 (a histone acetyltransferase). The levels of 2 markers for neural tube development, bone morphogenetic protein-4 (BMP4) and sonic hedgehog (Shh), were measured in amniotic fluid and serum using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The AFSCs from the woman pregnant with a fetus affected by myelomeningocele had higher levels of H3K4me2, H3K4me3, H3K27me2, and H3K27me3 and lower levels of KDM6B than the AFSCs from the women with healthy fetuses. The levels of H3K9ac, H3K18ac, and Gcn5 were also decreased in the woman with the fetus exhibiting myelomeningocele. In AFSCs from the woman carrying an anencephalic fetus, levels of H3K27me3, along with those of H3K9Ac, H3K18ac, and Gcn5, were increased, while that of KDM6B was decreased. Compared with the normal controls, the levels of BMP4 in amniotic fluid and serum from the woman with a fetus with myelomeningocele were increased, whereas levels of Shh were increased in the woman pregnant with a fetus displaying anencephaly.
  
  
  CONCLUSIONS
  The levels of epigenetic marks, such as H3K4me, H3K27me3, H3K9Ac, and H3K18A, in cultured AFSCs in combination with levels of key developmental proteins, such as BMP4 and Shh, are potential biomarkers for early detection and identification of NTDs in amniotic fluid and maternal serum.
authors: Division of Pediatric Neurosurgery, Developmental Biology Program, Ann and Robert H. Lurie Children's Hospital of Chicago Research Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors: Takao
authors: T
authors: Tsurubuchi
authors: Shunsuke
authors: S
authors: Ichi
authors: Kyu-Won
authors: KW
authors: Shim
authors: William
authors: W
authors: Norkett
authors: Elise
authors: E
authors: Allender
authors: Barbara
authors: B
authors: Mania-Farnell
authors: Tadanori
authors: T
authors: Tomita
authors: David G
authors: DG
authors: McLone
authors: Norman
authors: N
authors: Ginsberg
authors: C Shekhar
authors: CS
authors: Mayanil
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000166:cytology / Q000378:metabolism*; D000757:Anencephaly / Q000175:diagnosis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D004677:Encephalocele / Q000175:diagnosis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D044127:Epigenesis, Genetic; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D008591:Meningomyelocele / Q000175:diagnosis / Q000378:metabolism; D009436:Neural Tube Defects / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D013234:Stem Cells / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D053823:Hedgehog Proteins; C509239:SHH protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human