Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple endpoints of spermatotoxicity in short duration tests (1-5 days exposure; 2.5-week assay interval) were investigated in a number of chemicals reported to produce minimal to severe reproductive effects when administered subchronically. Six of these chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced substantial spermatotoxicity after 1 to 5 doses. Spermatotoxic effects of chlordimeform were equivocal while p,p'-DDT, n-hexane, and sodium chlorite were judged negative. Four chemicals with known acute effects (benomyl, busulfan, ethylene glycol monomethyl ether, nitrobenzene) elicited expected histopathologic responses after a single dose. Testicular histology, testicular sperm head counts, cauda sperm counts, sperm morphology, and sperm velocity proved to be the most toxicologically sensitive endpoints in one or more of the studies, but histopathology of the testis and epididymis was the most consistent indicator of reproductive damage. The percentage of motile sperm and sperm concentration in the epididymal fluid were the least sensitive measurements. The data suggested that most chemicals with the potential to produce moderate to severe sperm damage are detectable with a short duration test. Complementary multiple endpoints enhanced the interpretation of results, often identified cellular targets, and provided insight on possible mechanisms. Specific responses were often similar to specific effects reported for subchronic exposures. A short duration test could be of value as a screen in structure-activity studies or to set priorities for chemicals requiring further evaluation. As a supplement to breeding studies, the data generated in the short test could also be used to enhance the design and interpretation of the longer tests.
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PMID:Endpoints of spermatotoxicity in the rat after short duration exposures to fourteen reproductive toxicants. 128 59

Charles River CD rats (approximate weight, 208 g) were exposed to 1.0% 2,5-hexanedione (2,5-HD) in drinking water for 5 weeks. Rats were killed 27, 60, and 75 weeks after exposure to evaluate the recovery potential following testicular injury. At 27 weeks, normal serum testosterone and significantly elevated serum luteinizing hormone and serum follicle-stimulating hormone levels were found in treated rats. The 2,5-HD-treated rats had low testicular and epididymal weights at all time points (28% and 72% of controls, respectively, at 75 weeks). Microscopically, there was a generalized loss of postspermatogonial germ cells at all time points, with no seminiferous tubules exhibiting normal spermatogenesis at 75 weeks. However, a relatively constant population of 3.1 to 3.7 spermatogonia/100 Sertoli cells was found in atrophic seminiferous tubules at all time points. The presence of a constant residual population of type A spermatogonia without a normal mass of more mature germ cells and the observed hormonal alterations suggest that 2,5-HD intoxication produced a lengthy disruption in local testicular homeostatic mechanisms that control spermatogenesis.
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PMID:2,5-hexanedione exposure in the rat results in long-term testicular atrophy despite the presence of residual spermatogonia. 201 Mar 48