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

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 stern cells. A statistically significant increase in mWAPL expression was observed at 0.1 mum TCDD in AhR(-/-) mouse embryonic fibroblast cells. Interestingly at 1 mum TCDD, in WAPL 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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.