Effects of Vinclozolin Administration on Sperm Production and Testosterone Biosynthetic Pathway in Adult Male Rat
Journal of Reproduction and Development, Vol. 49, No. 5, 2003 —Original— Effects of Vinclozolin Administration on Sperm Production and Testosterone Biosynthetic Pathway in Adult Male Rat Kunihiro KUBOTA1,5), Seiichiroh OHSAKO1,5), Shuichi KUROSAWA3), Ken TAKEDA3), Wu QING1,5), Motoharu SAKAUE4), Takashige KAWAKAMI3), Ryuta ISHIMURA1,5) and Chiharu TOHYAMA2,5) 1)Molecular and Cellular Toxicology Section, and 2)Environmental Health Sciences Division, National Institute for Environmental Studies, 16–2 Onogawa, Tsukuba, Ibaraki 305-0053, 3)Laboratory of Hygienic Chemistry, Science University of Tokyo, 12 Ichigaya- Funagawaramachi, Shinjuku-ku, Tokyo 162-0826, 4)Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo 108-8641, 5)CREST, JST, Kawaguchi, Saitama 332-0012, Japan Abstract. The effect of vinclozolin (VCZ), used as a fungicide and known to have anti-androgenic effects on spermatogenesis and gene expression in the male rat testis was investigated. In Experiment 1, VCZ (100 mg/kg/day) or flutamide (FM, 25 mg/kg/day) was orally administered to male Holzman rats for six days. 8 days after the last administration (D8), a drastic increase in intratesticular testosterone was detected in FM (4.2-fold over control) but not in VCZ treated animals, whereas on D36 post-administration, both groups showed similar levels. Significant decreases in daily sperm production were seen in both VCZ and FM-treated rats on D36. Semiquantitative RT-PCR analysis with testicular and pituitary mRNAs on D8 revealed that LHβ and FSHβ mRNAs were increased in the pituitary by VCZ, as well as by FM. Among the four testicular steroidogenic enzyme genes, cytochrome P450 side chain cleavage (P450scc) and cytochrome P450 17α/C17-20 lyase (P450c17) mRNAs were significantly increased, whereas 17β-hydroxysteroid dehydrogenase type III (17βHSD) mRNA was not changed.
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