Epigenetic assessment of environmental chemicals detected in maternal peripheral and cord blood samples

Yoshikazu Arai, Jun Ohgane, Shintaro Yagi, Rie Ito, Yusuke Iwasaki, Koichi Saito, Kazuhiko Akutsu, Satoshi Takatori, Rie Ishii, Rumiko Hayashi, Shun Ichiro Izumi, Norihiro Sugino, Fumio Kondo, Masakazu Horie, Hiroyuki Nakazawa, Tsunehisa Makino, Kunio Shiota*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Epigenetic alteration is an emerging paradigm underlying the long-term effects of chemicals on gene functions. Various chemicals, including organophosphate insecticides and heavy metals, have been detected in the human fetal environment. Epigenetics by DNA methylation and histone modifications, through dynamic chromatin remodeling, is a mechanism for genome stability and gene functions. To investigate whether such environmental chemicals may cause epigenetic alterations, we studied the effects of selected chemicals on morphological changes in heterochromatin and DNA methylation status in mouse ES cells (ESCs). Twenty-five chemicals, including organophosphate insecticides, heavy metals and their metabolites, were assessed for their effect on the epigenetic status of mouse ESCs by monitoring heterochromatin stained with 4′,6-diamino-2-phenylindole (DAPI). The cells were surveyed after 48 or 96 h of exposure to the chemicals at the serum concentrations of cord blood. The candidates for epigenetic mutagens were examined for the effect on DNA methylation at genic regions. Of the 25 chemicals, five chemicals (diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se) and octachlorodipropyl ether (S-421)) caused alterations in nuclear staining, suggesting that they affected heterochromatin conditions. Hg and Se caused aberrant DNA methylation at gene loci. Furthermore, DEP at 0.1 ppb caused irreversible heterochromatin changes in ESCs, and DEP-, Hg- and S-421-exposed cells also exhibited impaired formation of the embryoid body (EB), which is an in vitro model for early embryos. We established a system for assessment of epigenetic mutagens. We identified environmental chemicals that could have effects on the human fetus epigenetic status.

Original languageEnglish
Pages (from-to)507-517
Number of pages11
JournalJournal of Reproduction and Development
Issue number4
Publication statusPublished - 2011
Externally publishedYes


  • DNA methylation
  • Embryoid body
  • Epigenetic mutagens
  • Es cells
  • Heterochromatin

ASJC Scopus subject areas

  • Animal Science and Zoology


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