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Published on: May 2, 2017
Occurrence of multinucleated hepatocytes in cynomolgus monkeys (Macaca fascicularis) from different geographical
M N Novilla1, M K Jackson2, D A Reim3
1Shin Nippon Biomedical Research Laboratories, Everett, WA, USA mnovilla@snblusa.com.
Abstract:
Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is sparse on variations in incidence in the cynomolgus macaque (Macaca fascicularis). A survey was conducted to assess the occurrence of MNHs in the liver of stock (nonstudy) animals from SNBL SRC (Alice, TX) and SNBL USA (Everett, WA) submitted for diagnostic purposes. A total of 215 cynomolgus monkeys originally from Cambodia (61), China (5), Indonesia (125), and Mauritius (24) were used for this investigation. From each animal, usually 2 liver samples were processed for histopathology with 2 sections in each slide. An MNH was defined as a hepatocyte with 3 or more nuclei. A threshold of 3 MNHs was selected for the Multinucleated Hepatocyte Grading System: 0 = not remarkable (≤3 MNHs counted from 2-4 liver sections), minimal = 4 to 15 MNHs, mild = 16 to 30 MNHs, moderate = 31 to 59 MNHs, and severe ≥60 MNHs. The incidence of MNHs was 60 of 86 (70%) in males and 72 of 129 (56%) in females for a total overall incidence of 132 of 215 animals (61%). Affected hepatocytes were frequently observed close to the capsule and generally had 3 to 8 nuclei per hepatocyte but as many as 15 occurred in a single cell. Awareness of the incidence of MNHs in cynomolgus monkeys is important for potential use as background data in preclinical safety and toxicity evaluation studies.
Insights
Multinucleated hepatocytes (MNHs) are common in cynomolgus monkeys, with a 61% incidence observed. This finding is crucial background data for preclinical safety and toxicity studies in nonhuman primates.
Area of Science:
- Veterinary Pathology
- Toxicology
- Primate Research
Background:
- Multinucleated hepatocytes (MNHs) are occasionally found in nonhuman primates but data on incidence in cynomolgus macaques is limited.
- Understanding MNH incidence is vital for interpreting histopathology in preclinical safety studies.
Purpose of the Study:
- To survey the occurrence and incidence of MNHs in cynomolgus macaques (Macaca fascicularis).
- To establish a grading system for MNHs based on their frequency in liver tissue.
Main Methods:
- Histopathological examination of liver samples from 215 cynomolgus monkeys from various origins.
- Defined MNHs as hepatocytes with three or more nuclei and developed a grading system (0 to severe).
Main Results:
- Overall incidence of MNHs was 61% (132/215 animals).
- Incidence was higher in males (70%) than females (56%).
- Affected hepatocytes often had 3-15 nuclei and were located near the liver capsule.
Conclusions:
- MNHs are a common finding in cynomolgus monkeys, with significant variation by sex.
- This data provides essential baseline information for preclinical toxicology and safety evaluations using this species.
