Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys

Broberg, Karin (author), Ahmed, S. (author), Engström, Karin (author), Hossain, Mohammad Bakhtiar (author), Jurković Mlakar, Simona (author), Bottai, Matteo (author), Grandér, M. (author), Raqib, Rubhana (author), Vahter, Marie (author)

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov–Smirnov test, P-value<10$^{–15}$), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r$_s$-values>−0.62), but in girls only 207 (41%) showed inverse correlation (r$_s$>-values>−0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.

• Language: English
• Keywords: 450 K, cancer, CpG, development, epigenetic, fetal
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 288-298
• Numbering: Vol. 5, no. 4
• PID: 20.500.12556/RUL-165841
• UDC: 661.8'046:612.63
• ISSN on article: 2040-1752
• DOI: 10.1017/S2040174414000221 P
• COBISS.SI-ID: 215871235
• Publication date in RUL: 12.12.2024

Record is a part of a journal

• Title: Journal of developmental origins of health and disease
• Publisher: Cambridge University Press
• ISSN: 2040-1752
• COBISS.SI-ID: 522548249

Licences

• License: CC BY 3.0, Creative Commons Attribution 3.0 Unported
• Link: https://creativecommons.org/licenses/by/3.0/deed.en
• Description: You are free to reproduce and redistribute the material in any medium or format. You are free to remix, transform, and build upon the material for any purpose, even commercially. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.

Secondary language

• Language: Slovenian
• Keywords: nosečnost, arzenove spojine, 450 K, rak (medicina), CpG, epigenetika