Affiliation:
1. SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, Pennsylvania 19406
Abstract
Spontaneous testicular lesions were assessed in 50 control purpose-bred male beagle dogs. They were selected from 13 toxicology studies conducted over the period 1988-1999. Age of the dogs at study termination varied from 8-20 months with an average age of 13 months. Regardless of age, the most significant finding was bilateral segmental hypospermatogenesis in 15/50 (30%) of the dogs. Cross sections of tubules with hypospermatogenesis were distributed randomly throughout the testes and were characterized by reduced proportions of germ cells, tubular shrinkage, and Sertoli cell prominence. These changes were occasionally associated with giant cells, with cellular debris, and in 6/15 (40%) with atrophic tubules devoid of germ cells, indicating a degenerative process. Focal subcapsular tubular atrophy or hypoplasia (tubules lined by Sertoli cells only) was also found in 9/35 (26%) of dogs without hypospermatogenesis. Inhibited spermiation with retention of mature sperm in tubules was seen in 6/50 dogs, 3 of which also showed hypospermatogenesis. Other findings of high incidence but low prevalence included tubules with multinucleated giant cells, swollen spermatocytes, or apoptotic germ cells. These latter changes are probably a constituent of normal spermatogenesis. In conclusion, about 30% of control beagle dogs show segmental hypospermatogenesis, which may be associated with degenerative changes, and an additional 18% of the dogs exhibit focal tubular atrophy/hypoplasia in otherwise normal testes. These changes have to be distinguished from compound-related toxic effects.
Subject
Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine
Cited by
36 articles.
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