Aging, Environment, & DiseaseDNA Methylation and Hydroxymethylation

Sex-specific Alterations in DNA Methylation from Prenatal Exposure to Seafood Toxins

Seafood toxins in the wombExposure to toxins in the womb can alter DNA methylation in the offspring [1], [2], persisting after birth [3]. Changes in DNA methylation in umbilical cord white blood cells (UCWBCs) have been linked to increased prevalence of disease, such as asthma [4]. To date, studies have dealt with a single toxin at a time. This does not translate well to nature where people can encounter multiple toxins at a time such as when consuming seafood. Leung et al used a birth cohort from the Faroe Islands, a population known to consume large amounts of seafood contaminated with toxins, to study the complex epigenetic effects of multi-toxin exposure en utero [5], [6].

In this paper, Leung studied several toxins including methylmercury (MeHg), hexachlorobenzene (HCB), p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), perfluorooctanesulfonic acid (nPFOS) and PCB congener 105 (CB-105). When looking at all the subjects, CB-105 had the largest influence on DNA methylation. DNA methylation also changed in a female-specific manner after CB-105 exposure at 73 CpGs. 13 of the genes effected by CB-105 exposure were related to the ELAV1-associated cancer network.

In males, CpG methylation changes in UCWBCs were associated with exposure to nPFOS, HCB, and p,p’-DDE. Alterations in CpG methylation were disproportionately found on the X-chromosome (15-25%), compared to the somatic chromosomes (4.2-4.6%). There was less than 50% overlap between methylation sites associated with nPFOS, HCB, or p,p’-DDE exposure in UCWBC. As a result, these toxins are linked to functional changes in different systems. For example, HCB and p,p’-DDE exposure affected reproductive system development and function, while nPFOS or p,p’-DDE exposure affects nervous system development and function.

Leung et al found that exposure to toxins from seafood in the womb can have different effects on males and females after birth. Female DNA methylation was altered after exposure to CB-105, and males were affected by nPFOS, HCB, and p,p’-DDE exposure. These sex-dependent differences resulted in distinct toxin effects in females and males.

Original Article

  1. Y.-K. Leung et al., “Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort.,” Epigenetics, pp. 1–32, Mar. 2018.

References

  1. W. Tang et al., “Maternal exposure to polycyclic aromatic hydrocarbons and 5’-CpG methylation of interferon-γ in cord white blood cells.,” Environmental health perspectives, vol. 120, no. 8, pp. 1195–1200, Aug. 2012.
  2. B. R. Joubert et al., “450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.,” Environmental health perspectives, vol. 120, no. 10, pp. 1425–1431, Oct. 2012.
  3. J. R. Pilsner et al., “Influence of prenatal lead exposure on genomic methylation of cord blood DNA.,” Environmental health perspectives, vol. 117, no. 9, pp. 1466–1471, Sep. 2009.
  4. F. Perera et al., “Relation of DNA methylation of 5’-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma.,” PloS one, vol. 4, no. 2, p. e4488, Feb. 2009.
  5. P. Grandjean et al., “Methylmercury exposure biomarkers as indicators of neurotoxicity in children aged 7 years.,” Am. J. Epidemiol., vol. 150, no. 3, pp. 301–305, Aug. 1999.
  6. P. Grandjean et al., “Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.,” Neurotoxicology and teratology, vol. 23, no. 4, pp. 305–317, Aug. 2001.
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Aaron Barnett

Aaron Barnett