title: Light microscopic and ultrastructural pathology of seminiferous tubules of rats given multiple doses of Pasteurella multocida group D protein toxin.
abstract: Male Holtzman rats were given subcutaneous doses of a purified Pasteurella multocida group D heat-labile toxin on alternate days for up to 22 days. Rats were necropsied at 18 days or 36 days (14 days after last dose of toxin) or when moribund, and testicles were taken for histologic and ultrastructural examination. Other selected tissues, including liver and spleen, were taken for histologic examination. Histologically, testicular and splenic lesions occurred more consistently and at much smaller doses when compared with lesions in other target organs such as liver. Testicular and splenic lesions were present in all rats (6/6) given 0.8 micrograms/kg toxin and were seen in some rats (1/6) given as little as 0.2 micrograms/kg toxin. Only 3/6 rats given 0.8 micrograms/kg toxin had hepatic lesions; no hepatic lesions were seen at doses of 0.2 micrograms/kg. Testicles from toxin-treated rats were smaller and weighed less than controls. Seminiferous tubules were moderately dilated and lined by polygonal sertoli cells. The normal spermatogenic maturation sequence and mature spermatids were absent, and many tubules contained multinucleate spermatocytes. Severely affected tubules were necrotic and mineralized. Ultrastructurally, there was necrosis of adluminal spermatocytes, multinucleate cell formation, and spaces between Sertoli cell plasma membranes. Testicular lesions were similar to those described for vitamin D-deficient rats, vitamin A-deficient rats, vasectomized rats, and rats given intravenous tumor necrosis factor; however, rats given lethal doses of toxin did not have elevated levels of TNF alpha activity.
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, Iowa 50010.
authors.forename: M R
authors.initials: MR
authors.lastname: Ackermann
authors.forename: J P
authors.initials: JP
authors.lastname: Tappe
authors.forename: J R
authors.initials: JR
authors.lastname: Thurston
authors.forename: R B
authors.initials: RB
authors.lastname: Rimler
authors.forename: D E
authors.initials: DE
authors.lastname: Shuster
authors.forename: N F
authors.initials: NF
authors.lastname: Cheville
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity*; D006651:Histocytochemistry; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D016979:Pasteurella multocida; D051381:Rats; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D012708:Sertoli Cells / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013154:Spleen / Q000473:pathology; D013737:Testis / Q000473:pathology / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C062258:Pasteurella multocida toxin; D014409:Tumor Necrosis Factor-alpha