title: Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.
abstract: BACKGROUND
  Pregnancy induces physiological adaptations that may involve, or contribute to, alterations in the genomic landscape. Pregnancy also increases the nutritional demand for choline, an essential nutrient that can modulate epigenomic and transcriptomic readouts secondary to its role as a methyl donor. Nevertheless, the interplay between human pregnancy, choline and the human genome is largely unexplored.
  
  
  RESULTS
  As part of a controlled feeding study, we assessed the influence of pregnancy and choline intake on maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26-29 gestation) and nonpregnant (n = 21) women were randomized to choline intakes of 480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks. Blood leukocytes were acquired at study week 0 and study week 12 for microarray, DNA damage and global DNA/histone methylation measurements. A main effect of pregnancy that was independent of choline intake was detected on several of the maternal leukocyte genomic markers. Compared to nonpregnant women, third trimester pregnant women exhibited higher (P<0.05) transcript abundance of defense response genes associated with the innate immune system including pattern recognition molecules, neutrophil granule proteins and oxidases, complement proteins, cytokines and chemokines. Pregnant women also exhibited higher (P<0.001) levels of DNA damage in blood leukocytes, a genomic marker of oxidative stress. No effect of choline intake was detected on the maternal leukocyte genomic markers with the exception of histone 3 lysine 4 di-methylation which was lower among pregnant women in the 930 versus 480 mg/d choline intake group.
  
  
  CONCLUSIONS
  Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States of America.
authors.forename: Xinyin
authors.initials: X
authors.lastname: Jiang
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Bar
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Allyson A
authors.initials: AA
authors.lastname: West
authors.forename: Cydne A
authors.initials: CA
authors.lastname: Perry
authors.forename: Olga V
authors.initials: OV
authors.lastname: Malysheva
authors.forename: Srisatish
authors.initials: S
authors.lastname: Devapatla
authors.forename: Eva
authors.initials: E
authors.lastname: Pressman
authors.forename: Francoise M
authors.initials: FM
authors.lastname: Vermeylen
authors.forename: Martin T
authors.initials: MT
authors.lastname: Wells
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D016000:Cluster Analysis; D004249:DNA Damage; D004032:Diet; D057890:Epigenomics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D023281:Genomics; D006657:Histones / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018384:Oxidative Stress; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D006657:Histones; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002794:Choline