Abstract
Exposure to chemicals and environmental pollutants among them cadmium, lead, and mercury can harm reproduction. The metals cross the placenta, accumulate in placental tissue, and pass onto fetal blood and fetal organs to variable amounts. Still, the mechanisms underlying their transplacental passage are largely unknown and the human placenta is the most poorly understood organ in terms of reproduction toxicology. The genetic factors modulating placental toxicokinetics remain unclear just as well. From a genetic perspective, three aspects, which influence capacities of the human placenta to metabolize and transport toxicants, need to be considered. These are 1/presence and interplay of two genotypes, 2/chromosomal aberrations including aneuploidies and sequence variations, and 3/epigenetics and genetic imprinting. In this review, we summarize the current state of knowledge on how genetics and epigenetics affect placental (patho)physiology and thus fetal development and health.
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Notes
Online document: http://echa.europa.eu/web/guest/candidate-list-table. Accessed 26 May 2016.
BeWo is a human trophoblast-derived choriocarcinoma cell line widely used to study the syncytiotrophoblast as the cells can be stimulated to differentiate and fuse in vitro.
CpG stands for 5′-C-phosphate-G-3′ regions of DNA, where a cytosine is followed by a guanine nucleotide linked by one phosphate. The term is used to distinguish CG pairs of linear sequences from CG base pairs in double-stranded DNA.
One famous example is the epigenetic regulation of the agouti gene (Yen et al. 1994). Maternal methyl-donor supplementation during pregnancy with folic acid, vitamin B12, choline and betaine was shown to affect the phenotype of the Avy (viable yellow agouti) offspring by directly altering the epigenome.
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Gundacker, C., Neesen, J., Straka, E. et al. Genetics of the human placenta: implications for toxicokinetics. Arch Toxicol 90, 2563–2581 (2016). https://doi.org/10.1007/s00204-016-1816-6
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DOI: https://doi.org/10.1007/s00204-016-1816-6