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BMC Pharmacol Toxicol. 2015 Jul 15;16:20. doi: 10.1186/s40360-015-0020-2.

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight.

Author information

1
Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. adriana.vidal@cshs.org.
2
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA. vika245@gmail.com.
3
Department of Public Health, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA. vika245@gmail.com.
4
Division of Water, Climate, and the Environment, School of Earth Sciences, The Ohio State University, Columbus, OH, 43210, USA. darrah.24@osu.edu.
5
Nicholas School of the Environment, Duke University, Research Drive, Durham, NC, 27710, USA. vengosh@duke.edu.
6
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Research Drive, Durham, NC, 27710, USA. zhiqing.huang@duke.edu.
7
Environmental Public Health Division, U.S. Environmental Protection Agency, Chapel Hill, NC, 27599, USA. katherine.king@duke.edu.
8
Department of Community and Family Medicine and Duke Cancer Institute, Duke University School of Medicine, Erwin Drive, Durham, NC, 27710, USA. katherine.king@duke.edu.
9
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Research Drive, Durham, NC, 27710, USA. mnye@email.unc.edu.
10
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, 450 West Drive, Chapel Hill, NC, 27599, USA. mnye@email.unc.edu.
11
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, UNC-Chapel Hill, Chapel Hill, NC, 27599, USA. rfry@unc.edu.
12
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA. daskaar@ncsu.edu.
13
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA. rlmaguir@ncsu.edu.
14
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University School of Medicine, Erwin Drive, Durham, NC, 27710, USA. amy.murtha@duke.edu.
15
Department of Community and Family Medicine and Duke Cancer Institute, Duke University School of Medicine, Erwin Drive, Durham, NC, 27710, USA. joellen.schildkraut@duke.edu.
16
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Research Drive, Durham, NC, 27710, USA. susan.murphy@duke.edu.
17
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA. choyo@ncsu.edu.

Abstract

BACKGROUND:

Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited.

METHODS:

We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤ 12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight.

RESULTS:

Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05).

CONCLUSIONS:

Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required.

PMID:
26173596
PMCID:
PMC4502530
DOI:
10.1186/s40360-015-0020-2
[Indexed for MEDLINE]
Free PMC Article

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