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J.Health Sci., 55(6), 952-956, 2009

Decreased Gene Expression of Testicular Cell-Specific Proteins in Cadmium-Induced Acute Testicular Toxicity

Kiyomitsu Nemoto,*, a Shoji Miyajima,a Shiori Hara,a Ryosuke Saigusa,a Masaki Yamada,a Hiroshi Shikama,b Shuichi Yotsuya,b Masashi Sekimoto,a and Masakuni Degawaa

aDepartment of Molecular Toxicology and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan, and bCentral Research Institute, Ishihara Sangyo Kaisha, Ltd., 2-3-1 Nishi-Shibukawa, Kusatsu, Shiga 525-0025, Japan

Cadmium salts induce severe acute testicular necrosis in rodents. We assessed the expression levels of the genes encoding the follicle-stimulating hormone receptor, luteinizing hormone receptor, testisspecific histone 2B, and transition proteins 1 and 2, which are preferentially expressed in Sertoli cells, Leydig cells, spermatocytes, and spermatids, respectively, by reverse transcription (RT)-PCR using total RNA prepared from the whole testes of cadmium chloride (Cd)-administered rats. Spraque Dawley rats at 3, 7, and 12 weeks of age were singly and subcutaneously injected with Cd at doses of 1, 2.5, 5, 10, 15 or 20 μmol/kg. The expression levels of all genes tested were significantly decreased at doses of over 15 μmol/kg (3-week-old rats) or over 10 μmol/kg (7- and 12-week-old rats) 96 hr after injection. Histopathological study showed that these dosages of Cd resulted in extensive disruption of the seminiferous tubules and necrosis of testicular cells, while administration of Cd at a dose of 5 μmol/kg in 7- and 12-week-old rats resulted in only partial degeneration of seminiferous tubules and testicular cells. Therefore, their reduced gene expression is likely to serve as an indicator of Cd-induced testicular necrosis accompanied by cell death. In addition, the susceptibility to Cd-induced testicular damage and decreased gene expression was higher in mature (7- and 12-week-old) rats than in immature (3-week-old) rats.