title: Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.
abstract: OBJECTIVE
  One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women.
  
  
  METHODS
  This prospective pilot study included eight obese (BMI≥30) and eight lean (BMI<25) women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05). Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas.
  
  
  RESULTS
  In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold). Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu.
  
  
  CONCLUSIONS
  Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women.
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Edlow
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Neeta L
authors.initials: NL
authors.lastname: Vora
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hui
authors.affiliation: Department of Computer Science, Tufts University, Medford, Massachusetts, United States of America.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Wick
authors.affiliation: Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Cowan
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000649:Amniocentesis; D019295:Computational Biology; D005260:Female; D005333:Fetus / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008875:Middle Aged; D009035:Mothers; D009420:Nervous System / Q000196:embryology*; D009765:Obesity; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010865:Pilot Projects; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D055815:Young Adult