The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data

Abstract

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.

The Histology of Background Pathological Processes in Cynomolgus Monkeys (Macaca fascicularis) from Control Groups in Toxicology Studies

“…Accumulations of isolated siderophages were found in the cortical stroma in 1.4% of animals. Small lymphoplasmacytic infiltrates were most often found in the kidneys, which corresponded to the available literature data [5]. The prevalence How to cite this article:…”

“…The aim of this work was to describe the background histopathological findings in tissues from control cynomolgus monkeys received from the breeding facilities of the Sochi Research Institute of Medical Primatology, Russia, as well as primates imported from Vietnam. Since previous toxicology studies most often evaluated histological abnormalities in the internal organs of primates primarily from Mauritius, China and Vietnam, [5,6] it seems relevant to analyze the morphology of background lesions in monkeys used in preclinical studies conducted in the Russian Federation, followed by a comparative assessment between animals grown in the breeding facilities of Sochi and primates obtained from Vietnam.…”

Special Issue on the Pathobiology of Laboratory Nonhuman Primates: A Review of Species, Substrain, Geographical Origin, Age, and Modality-Related Factors

“…Conversely, Chinese macaques had higher incidences of inflammatory cell infiltrates in the gastrointestinal tract (GIT), gall bladder, and some salivary glands. 14 The authors concluded that the overall incidence of background pathology findings, the nature of the most common findings, and most commonly affected tissues were comparable among animals from the different geographical regions and that animals from all the geographical regions were suitable for use in toxicity testing. Routine clinical pathology parameters from cynomolgus macaques of mainland Asia origin (China, Vietnam, and Cambodia) and those from Mauritius were also compared.…”

“…Origin-associated differences were also observed in the incidence of spontaneous pathology and clinical pathology reference values between Mauritian Island cynomolgus macaques and mainland Asian animals. 13 Chamanza et al (2022) 14 carried out what is as of to date the largest, multisite and multi-continental, comparative analysis of the influence of geographical origin, age, sex, and animal husbandry practices on the spontaneous pathology of Asian (Chinese, Vietnamese, and Cambodian) and Mauritian macaques. Their findings were largely in alignment with those reported for other toxicology endpoints.…”

Comparison of Routine Hematology, Coagulation, and Clinical Chemistry Parameters of Cynomolgus Macaques of Mauritius Origin With Cynomolgus Macaques of Cambodia, China, and Vietnam Origin

“…4 Genetic diversity between Asian and Mauritius macaques has been observed and described in the literature. 3,5,6 Mauritius macaques have a more homogenous genetic pool than mainland Asia origin macaques, are devoid of herpes B virus, respond differently to immune system challenges, and have lower incidences of background pathology based on previously published literature 1,3,[5][6][7][8] although a recent study 9 reports these lower incidences depend on the tissues and/or organs sampled with a higher incidence of inflammatory infiltrates identified in some tissues when Mauritius origin macaques were compared with other origin macaques.…”