RESUMEN
To investigate the influence of geographical origin, age, and sex on toxicologically relevant spontaneous histopathology findings in cynomolgus macaques (Macaca fascicularis), we performed a comparative analysis of historical control data (HCD) from 13 test sites that included 3351 animals (1645 females and 1706 males) sourced from Mauritius, China, Vietnam, and Cambodia, aged from 2 to 9.5 years, and from 446 toxicology studies evaluated between 2016 and 2021. The most common findings were mononuclear infiltrates in the kidney, liver, brain, and lung, which showed highest incidences in Mauritian macaques, and heart, salivary glands, and gastrointestinal tract (GIT), which showed highest incidences of mononuclear infiltrates in mainland Asian macaques. Developmental and degenerative findings were more common in Mauritian macaques, while lymphoid hyperplasia and lung pigment showed higher incidences in Asian macaques. Various sex and age-related differences were also present. Despite origin-related differences, the similarities in the nature and distribution of background lesions indicate that macaques from all geographical regions are suitable for toxicity testing and show comparable lesion spectrum. However, in a toxicity study, it is strongly recommended to use animals from a single geographical origin and to follow published guidelines when using HCD to evaluate and interpretate commonly diagnosed spontaneous lesions.
Asunto(s)
Crianza de Animales Domésticos , Animales , China , Femenino , Macaca fascicularis , Masculino , Mauricio , VietnamRESUMEN
Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.
Asunto(s)
Enfermedades de los Monos/congénito , Epitelio Seminífero/patología , Enfermedades Testiculares/congénito , Animales , Cruzamiento , China , Colágeno/metabolismo , Incidencia , Macaca fascicularis/anatomía & histología , Masculino , Maduración Sexual , Pruebas de Toxicidad , VietnamRESUMEN
Vascular injury can be induced by different classes of drug candidates, and it can affect the mesenteric vasculature. Sampling of the mesenteric vessels in the rat is crucial for proper assessment of potential adverse or pharmacologic effects of drugs in nonclinical rodent studies. To date, several sampling and processing techniques for the histopathologic evaluation of the mesenteric artery in rodents have been described and used in studies with candidate drugs that may affect the vascular system. However, most of those techniques require a significant amount of time and effort. A less labor-intensive, time-consuming, and expensive technique that allows examination of the mesentery vasculature with abundant longitudinal and cross sections of the vessels when examined microscopically was developed and presented here.