TitleCord blood DNA methylation of DNMT3A mediates the association between in utero arsenic exposure and birth outcomes: Results from a prospective birth cohort in Bangladesh
Publication TypeJournal Article
Year of Publication2020
AuthorsBozack, AK, Cardenas, A, Geldhof, GJ, Quamruzzaman, Q, Rahman, M, Mostofa, G, Christiani, DC, Kile, ML
JournalEnvironmental Research
Volume183
Pagination109134
Date Published01/2020
ISSN00139351
Abstract
 

Highlights

  • The DNA methyltransferase DNMT3A is involved fetal epigenetic programming.
  • In utero arsenic levels were associated with greater methylation of CpGs in DNMT3A.
  • DNMT3A DNAm may be a mediator between in utero arsenic and worse birth outcomes.

Background

Fetal epigenetic programming plays a critical role in development. DNA methyltransferase 3 alpha (DNMT3A), which is involved in de novo DNA methylation (DNAm), is a prime candidate gene as a mediator between prenatal exposures and birth outcomes. We evaluated the relationships between in utero arsenic (As) exposure, birth outcomes, and DNMT3A DNAm.

Methods

In a prospective Bangladeshi birth cohort, cord blood DNAm of three DNMT3A CpGs was measured using bisulfite pyrosequencing. Maternal toenail As concentrations at birth were measured to estimate in utero exposure. Among vaginal births (N = 413), structural equation models (SEMs) were used to evaluate relationships between DNMT3A methylation, log2 (toenail As), birth weight, and gestational age.

Results

In an adjusted SEM including birth weight and gestational age, maternal toenail As levels were associated with DNMT3A DNAm (B = 0.40; 95% CI: 0.15, 0.66) and gestational age (B = −0.19 weeks; 95% CI: 0.36, −0.03). DNMT3A DNAm was associated with gestational age (B = −0.10 weeks; 95% CI: 0.16, −0.04) and birth weight (B = −11.0 g; 95% CI: 21.5, 0.4). There was an indirect effect of As on gestational age mediated through DNMT3A DNAm (B = −0.04; 95% CI: 0.08, −0.01), and there were indirect effects of maternal toenail As levels on birth weight through pathways including gestational age (B = −14.4 g; 95% CI: 29.2, −1.9), DNMT3A DNAm and gestational age (B = −3.1 g; 95% CI: 6.6, −0.8), and maternal weight gain and gestational age (B = −5.1 g; 95% CI: 9.6, −1.5). The total effect of a doubling in maternal toenail As concentration is a decrease in gestational age of 2.1 days (95% CI: 0.9, 3.3) and a decrease in birth weight of 29 g (95% CI: 14, 46).

Conclusions

DNMT3A plays a critical role in fetal epigenetic programming. In utero arsenic exposure was associated with greater methylation of CpGs in DNMT3A which partially mediated associations between prenatal As exposure and birth outcomes. Additional studies are needed to verify this finding.

DOI10.1016/j.envres.2020.109134
Short TitleEnvironmental Research