title: Fasciola hepatica: disruption of spermatogenesis by the fasciolicide compound alpha.
abstract: Sheep infected with the triclabendazole-susceptible Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48, and 72 h post-treatment (p.t.). Changes to the spermatogenic cells in the testis were examined by histology and transmission electron microscopy. Disruption to the testes became increasingly severe over time. The testis tubules shrank in size, became vacuolated, and contained fewer cells. Identification of cell types became difficult, and apoptotic eosinophilic bodies were the predominant feature at 72 h p.t. Changes to the spermatogonia were evident at 24 h p.t., the cells containing swollen and electron-lucent mitochondria. The proportion of tertiary spermatogonia increased at 48 h p.t., and they showed signs of autophagy. Multinucleate spermatogonia were a feature of drug treatment at this time point, and they contained autophagic vacuoles. By 72 h p.t., it was difficult to identify primary and secondary spermatogonia, and there were no recognisable clusters of tertiary spermatogonia. Most spermatogonial cells were multinucleate and in the process of breaking down. With regard to the primary spermatocytes, fragmentation of the cytophore was observed at 24 h p.t. Intact rosettes were rare after 48 h treatment; collections of cells were seen, but were not organised into clusters. By 72 h p.t., no spermatocyte cells could be recognised. The results indicate that spermatogenesis was severely affected by compound alpha.
authors.affiliation: Parasite Therapeutics Research Group, School of Biological Sciences, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, BT97BL Belfast, UK.
authors.forename: Maeve
authors.initials: M
authors.lastname: McConville
authors.forename: Robert E B
authors.initials: RE
authors.lastname: Hanna
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Brennan
authors.forename: Maurice
authors.initials: M
authors.lastname: McCoy
authors.forename: Hillary W J
authors.initials: HW
authors.lastname: Edgar
authors.forename: Shirley
authors.initials: S
authors.lastname: McConnell
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Ian
authors.initials: I
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005210:Fasciola hepatica / Q000187:drug effects*; D005211:Fascioliasis / Q000188:drug therapy / Q000662:veterinary*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy*; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000473:pathology
chemical_list: C468032:5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole; D000871:Anthelmintics; D007093:Imidazoles; D009281:Naphthalenes