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 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.
Kuroda
Masahiko
M
Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. kuroda@tokyo-med.ac.jp
Oikawa
Kosuke
K
Ohbayashi
Tetsuya
T
Yoshida
Keiichi
K
Yamada
Kazuhiko
K
Mimura
Junsei
J
Matsuda
Yoichi
Y
Fujii-Kuriyama
Yoshiaki
Y
Mukai
Kiyoshi
K
D000595:Amino Acid Sequence; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D013090:Spermatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
D000072317:Polychlorinated Dibenzodioxins; D011506:Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C496335:WAPL protein, mouse; D019363:Cytochrome P-450 CYP1A1