Genetics of the human placenta: implications for toxicokinetics

Arch Toxicol. 2016 Nov;90(11):2563-2581. doi: 10.1007/s00204-016-1816-6. Epub 2016 Sep 6.

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.

Keywords: Aneuploidies; Epigenetics; Genotype; Imprinting; SNP; Sequence variation.

Publication types

  • Review

MeSH terms

  • Aneuploidy
  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Chromosome Aberrations / chemically induced
  • Chromosome Aberrations / embryology
  • Drug Resistance
  • Environmental Pollutants / metabolism
  • Environmental Pollutants / toxicity*
  • Epigenesis, Genetic* / drug effects
  • Female
  • Fetal Development / drug effects
  • Humans
  • Lead / metabolism
  • Lead / toxicity*
  • Maternal-Fetal Exchange / drug effects
  • Mercury / metabolism
  • Mercury / toxicity*
  • Placenta / drug effects*
  • Placenta / metabolism
  • Placentation / drug effects
  • Polymorphism, Genetic*
  • Pregnancy
  • Tissue Distribution
  • Toxicokinetics

Substances

  • Environmental Pollutants
  • Cadmium
  • Lead
  • Mercury