Molecular mechanism on the testicular toxicity of 1,3-dinitrobenzene in Sprague-Dawley rats: preliminary study.
The present study was conducted to elucidate the possible molecular mechanism of germinal cell apoptosis induced by Sertoli cell damage after 1,3-dinitrobenzene (1,3-DNB), a testicular toxicant, was administered to laboratory male rats. In this study, male Sprague-Dawley rats were administered with a single oral dose of 1,3-DNB (25 mg/kg body weight). Histopathological examinations and TUNEL methods revealed a marked increase in the number of apoptotic pachytene spermatocytes in seminiferous tubules showing stages VII-VIII and IX-XI of the spermatogenic cycle at 24 h after 1,3-DNB treatment. In immunohistochemical analysis, the cytoplasm and nuclei of pachytene spermatocytes were sometimes stained with antibodies to Bax and cleaved caspase-3 at 24 h after treatment. RT-PCR analysis for apoptosis-related gene expression showed that the expression of Bax,Bcl-2, Bcl-xL, and Bcl-xs genes, which are implicated in mitochondrial pathway, was significantly upregulated in the testes of the treated rats. These results suggest that the mitochondrial pathway is mainly involved in the testicular germinal cell apoptosis in rats induced by 1,3-DNB.
Muguruma
Masako
M
Laboratory of Veterinary Pathology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo 183-8509, Japan. muguruma@cc.tuat.ac.jp
Yamazaki
Masaki
M
Okamura
Miwa
M
Moto
Mitsuyoshi
M
Kashida
Yoko
Y
Mitsumori
Kunitoshi
K
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D004136:Dinitrobenzenes / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; D004136:Dinitrobenzenes; D012333:RNA, Messenger; C017906:3-dinitrobenzene