Abstract
Prenatal exposure to the highly toxic and common pollutant cadmium has been associated with adverse effects on child health and development. However, the underlying biological mechanisms of cadmium toxicity remain partially unsolved. Epigenetic disruption due to early cadmium exposure has gained attention as a plausible mode of action, since epigenetic signatures respond to environmental stimuli and the fetus undergoes drastic epigenomic rearrangements during embryogenesis. In the current review, we provide a critical examination of the literature addressing prenatal cadmium exposure and epigenetic effects in human, animal, and in vitro studies. We conducted a PubMed search and obtained eight recent studies addressing this topic, focusing almost exclusively on DNA methylation. These studies provide evidence that cadmium alters epigenetic signatures in the DNA of the placenta and of the newborns, and some studies indicated marked sexual differences for cadmium-related DNA methylation changes. Associations between early cadmium exposure and DNA methylation might reflect interference with de novo DNA methyltransferases. More studies, especially those including environmentally relevant doses, are needed to confirm the toxicoepigenomic effects of prenatal cadmium exposure and how that relates to the observed health effects of cadmium in childhood and later life.
Highlights
Exposure to CadmiumCadmium is ubiquitous in the environment
Lead, and methylmercury, which effectively cross the placental barrier in humans and other mammals leading to direct fetal exposure [6], cadmium is largely retained in the placenta, where it can accumulate to high concentrations [7, 8, 9]
T1/T3 first/third trimester of pregnancy, M median, AM arithmetic mean, GW gestational week, FFQ food frequency questionnaire, long interspersed nuclear element 1 (LINE-1) long interspersed nuclear element-1, 450 K Illumina Infinium Human Methylation 450, Methylated CpG island recovery assay (MIRA) methylated CpG island recovery assay; expression changes refer to the level of mRNA and/or protein
Summary
Exposure to the general population occurs mainly via intake of plantderived foods and certain types of seafood and through tobacco smoking and industrial emissions [1]. Women have higher internal levels of cadmium than men, likely as a result of higher gastrointestinal absorption of cadmium in women with low iron stores or due to genetic factors [2,3,4,5]. Pregnant women appear to accumulate more cadmium than nonpregnant women [4]. Lead, and methylmercury, which effectively cross the placental barrier in humans and other mammals leading to direct fetal exposure [6], cadmium is largely retained in the placenta, where it can accumulate to high concentrations [7, 8, 9].
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