Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women

PLoS One. 2012;7(11):e46736. doi: 10.1371/journal.pone.0046736. Epub 2012 Nov 2.


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.

Methodology/principal findings: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Case-Control Studies
  • Choline / metabolism
  • Cluster Analysis
  • DNA Damage*
  • Diet
  • Epigenomics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human
  • Genomics
  • Histones / metabolism
  • Humans
  • Immunity, Innate*
  • Interleukin-6 / biosynthesis
  • Leukocytes / metabolism
  • Leukocytes, Mononuclear / cytology
  • Oligonucleotide Array Sequence Analysis / methods
  • Oxidative Stress
  • Pregnancy
  • Pregnancy Trimester, Third
  • Transcriptional Activation*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Histones
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Choline

Grant support

This work was funded by the Egg Checkoff, through the Egg Nutrition Center; the Beef Checkoff, through the National Cattlemen's Beef Association and the Nebraska Beef Council; the United States Department of Agriculture Cooperative State Research, Education and Extension Service (CSREES), Special Research Grant No. 00444528; and the Affinito-Stewart Grants Program, through the President's Council of Cornell Women. The funding sources had no role in the study design, interpretation of the data and/or publication of the results.