Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on preimplantation mouse embryos

Toxicology. 2002 May 24;174(2):119-29. doi: 10.1016/s0300-483x(02)00047-1.


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental contaminant that can exert developmental toxicity. To investigate the stage-specific effects of TCDD on preimplantation embryos, we exposed mouse embryos to TCDD at different stages (1-, 2-, and 8-cell) and collected them at different stages of development (the 1- or 2-, 8-cell, and blastocyst stage, respectively). Semiquantitative RT-PCR revealed increased constitutive gene expression of the arylhydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) at the 1-cell stage, decreased expression at the 2- to 8-cell stage, and increased expression again at the blastocyst stage, and addition of TCDD to media did not affect their mRNA levels. Interestingly, no cytochrome P4501A1 (CYP1A1) mRNA was detected in embryos at the 1-, 2-, and 8-cell stages after exposure to 10 nM TCDD for 12 or 24 h, whereas CYP1A1 mRNA was significantly increased at the blastocyst stage in response to TCDD, and its induction was found to be concentration-dependent on TCDD exposure from 0.01 to 10 nM for 24 h. In addition, no significant differences in development rate of preimplantation embryos, cell number of blastocyst embryos, or apoptotic indices, such as TUNEL-positive cell number or Bax/Bcl-2 expression ratios were observed at the blastocyst stage between TCDD-exposed groups and non-exposed group. These results suggest that the sensitivity to TCDD differs with the embryonic stage, which may reflect an ability of embryos to adapt to environmental stressors, such as dioxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blastocyst / drug effects*
  • Cell Count
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A1 / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Polychlorinated Dibenzodioxins / toxicity*
  • Pregnancy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Aryl Hydrocarbon / biosynthesis
  • Receptors, Aryl Hydrocarbon / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Cytochrome P-450 CYP1A1