Abstract
BackgroundEvidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials.This study utilized a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/day) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n = 991) and blood leukocytes at 5 years (n = 667). Global DNA methylation was measured in all samples, and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years.ResultsThere were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect.ConclusionMaternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans and point the way for future studies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12605000569606 and ACTRN12611001127998 Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0281-7) contains supplementary material, which is available to authorized users.
Highlights
Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life
Global DNA methylation No significant differences in LINE1 hypomethylation levels were found between the control and DHAsupplemented groups either at birth or at 5 years of age (Table 2)
No probes were found to be significantly associated with cord blood docosahexaenoic acid (DHA) concentration when the analyses were performed separately by group or sex. In this large, well-characterized study population, we showed that maternal DHA supplementation across the second half of pregnancy was associated with modest alterations in DNA methylation in a small subset of genomic regions within genes involved in diverse biological
Summary
Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. DHA plays an important role in the development of the brain and central nervous system [15], and exposure to an increased DHA supply in utero has been associated, in some studies, with a reduced risk of allergy and improved metabolic health outcomes in postnatal life [16, 17]. The mechanisms underlying these effects are unclear; there have been suggestions that they may be epigenetically mediated
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