Maternal Obesity Affects Fetal Neurodevelopmental and Metabolic Gene Expression: A Pilot Study

• Published in: PloS one Vol. 9; no. 2; p. e88661
• Main Authors: Edlow, Andrea G., Vora, Neeta L., Hui, Lisa, Wick, Heather C., Cowan, Janet M., Bianchi, Diana W.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.02.2014; Public Library of Science (PLoS)
• Subjects: Abnormalities; Acids; Adult; Age; Amniocentesis; Amniotic fluid; Analysis; Apolipoproteins; Apoptosis; Biology; Body mass; Body mass index; Cell death; Central nervous system; Cerebral cortex; Cerebrum; Computational Biology; Epigenetics; Estrogens; Female; Fetus - embryology; Fetus - metabolism; Fetuses; Fos protein; Gene expression; Gene Expression Regulation, Developmental; Genes; Genomes; Genomics; Gestational age; Gynecology; Humans; Hybridization; Inflammation; Karyotypes; Laboratories; Medicine; Metabolic syndrome; Middle Aged; Molecular modelling; Morbidity; Mothers; Nervous System - embryology; Neurodevelopmental disorders; Obesity; Obstetrics; Offspring; Oligonucleotide Array Sequence Analysis; Organ Specificity; Pilot Projects; Pregnancy; Pregnancy Trimester, Second; Pregnant women; Regulators; Ribonucleic acid; RNA; Rodents; Signal transduction; Stat3 protein; Studies; Transcription activation; Womens health; Xenoestrogens; Young Adult; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088661

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. 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. 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. 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.