A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis

FEBS Lett. 2005 Jan 3;579(1):167-72. doi: 10.1016/j.febslet.2004.11.070.

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor that produces a variety of toxic effects. We have isolated a mouse homolog of the hWAPL gene, termed mouse WAPL (mWAPL), as a target of TCDD by cDNA representational difference analysis from mouse embryonic stem cells. A statistically significant increase in mWAPL expression was observed at 0.1 microM TCDD in AhR-/- mouse embryonic fibroblast cells. Interestingly, at 1 microM TCDD, mWAPL mRNA levels decreased in AhR+/+ cells, but further increased in AhR-/- cells. hWAPL and mWAPL were highly expressed only in testes among normal tissue samples, and we observed mWAPL localization in the synaptonemal complex of testicular chromosomes. In addition, mouse testes decreased the expression of mWAPL mRNA after a single intraperitoneal injection of TCDD. Thus, mammalian WAPL such as hWAPL and mWAPL may be involved in spermatogenesis and be target genes mediating the reproductive toxicity induced by TCDD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytochrome P-450 CYP1A1 / analysis
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Down-Regulation
  • Fibroblasts / chemistry
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Male
  • Mice
  • Molecular Sequence Data
  • Polychlorinated Dibenzodioxins / toxicity*
  • Proteins / analysis
  • Proteins / genetics*
  • Proteins / physiology*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / drug effects
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology
  • Sequence Alignment
  • Spermatocytes / chemistry
  • Spermatocytes / drug effects
  • Spermatocytes / metabolism
  • Spermatogenesis* / drug effects
  • Testis / cytology
  • Testis / drug effects
  • Testis / metabolism*
  • Up-Regulation

Substances

  • Polychlorinated Dibenzodioxins
  • Proteins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • WAPL protein, mouse
  • Cytochrome P-450 CYP1A1