Biology and Postnatal Development of Organ Systems of Cynomolgus Monkeys (Macaca Fascicularis)

Overview

Journal J Med Primatol

Publisher Wiley

Date 2022 Oct 27

PMID 36300896

Authors

Xiantang Li

Rosemary Santos

Jan E Bernal

Dingzhou D Li

Maureen Hargaden

Nasir K Khan

Affiliations

Soon will be listed here.

Abstract

Background: The cynomolgus macaque has become the most used non-human primate species in nonclinical safety assessment during the past decades.

Methods: This review summarizes the biological data and organ system development milestones of the cynomolgus macaque available in the literature.

Results: The cynomolgus macaque is born precocious relative to humans in some organ systems (e.g., nervous, skeletal, respiratory, and gastrointestinal). Organ systems develop, refine, and expand at different rates after birth. In general, the respiratory, gastrointestinal, renal, and hematopoietic systems mature at approximately 3 years of age. The female reproductive, cardiovascular and hepatobiliary systems mature at approximately 4 years of age. The central nervous, skeletal, immune, male reproductive, and endocrine systems complete their development at approximately 5 to 9 years of age.

Conclusions: The cynomolgus macaque has no meaningful developmental differences in critical organ systems between 2 and 3 years of age for use in nonclinical safety assessment.

Citing Articles

Differential effects of western versus mediterranean diets and psychosocial stress on ovarian function in female monkeys (Macaca fascicularis).

Frye B, Register T, Appt S, Vitolins M, Uberseder B, Chen H Psychoneuroendocrinology. 2023; 153:106107.

PMID: 37060654 PMC: 10225337. DOI: 10.1016/j.psyneuen.2023.106107.

Biology and postnatal development of organ systems of cynomolgus monkeys (Macaca fascicularis).

Li X, Santos R, Bernal J, Li D, Hargaden M, Khan N J Med Primatol. 2022; 52(1):64-78.

PMID: 36300896 PMC: 10092073. DOI: 10.1111/jmp.12622.

References

Sakamoto K, Sawada K, Fukunishi K, Noritaka I, Sakata-Haga H, Yoshihiro F . Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (Macaca fascicularis). Anat Rec (Hoboken). 2013; 297(2):200-7. DOI: 10.1002/ar.22847. View

Spoor M, Radi Z, Dunstan R . Characterization of age- and gender-related changes in the spleen and thymus from control cynomolgus macaques used in toxicity studies. Toxicol Pathol. 2008; 36(5):695-704. DOI: 10.1177/0192623308320279. View

Haruyama E, Ayukawa Y, Kamura K, Mizutamari M, Ooshima Y, Tanimoto A . Morphometric examination for development of reproductive organs in male cynomolgus monkeys. Toxicol Pathol. 2012; 40(6):918-25. DOI: 10.1177/0192623312444620. View

Akahori M, Takatori A, Kawamura S, Itagaki S, Yoshikawa Y . No regional differences of cytochrome P450 expression in the liver of Cynomolgus monkeys (Macaca fascicularis). Exp Anim. 2005; 54(2):131-6. DOI: 10.1538/expanim.54.131. View

Jarvis P, Srivastav S, Vogelwedde E, Stewart J, Mitchard T, Weinbauer G . The cynomolgus monkey as a model for developmental toxicity studies: variability of pregnancy losses, statistical power estimates, and group size considerations. Birth Defects Res B Dev Reprod Toxicol. 2010; 89(3):175-87. DOI: 10.1002/bdrb.20234. View

Sawada K, Fukunishi K, Kashima M, Saito S, Sakata-Haga H, Aoki I . Fetal gyrification in cynomolgus monkeys: a concept of developmental stages of gyrification. Anat Rec (Hoboken). 2012; 295(7):1065-74. DOI: 10.1002/ar.22478. View

Jayo M, Jerome C, Lees C, Rankin S, WEAVER D . Bone mass in female cynomolgus macaques: a cross-sectional and longitudinal study by age. Calcif Tissue Int. 1994; 54(3):231-6. DOI: 10.1007/BF00301684. View

Koyanagi T, Nakanishi Y, Murayama N, Yamaura Y, Ikeda K, Yano K . Age-related changes of hepatic clearances of cytochrome P450 probes, midazolam and R-/S-warfarin in combination with caffeine, omeprazole and metoprolol in cynomolgus monkeys using in vitro-in vivo correlation. Xenobiotica. 2014; 45(4):312-21. DOI: 10.3109/00498254.2014.979271. View

Li R, Wang H, Yang L, Zhang B, Li Y, Hu J . The whole mitochondrial genome of the Cynomolgus macaque (Macaca fascicularis). Mitochondrial DNA. 2013; 26(2):284-6. DOI: 10.3109/19401736.2013.825777. View

10.

Skaggs H, Chellman G, Collinge M, Enright B, Fuller C, Krayer J . Comparison of immune system development in nonclinical species and humans: Closing information gaps for immunotoxicity testing and human translatability. Reprod Toxicol. 2019; 89:178-188. DOI: 10.1016/j.reprotox.2019.06.005. View

11.

Aizawa K, Ageyama N, Yokoyama C, Hisatsune T . Age-dependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys. Exp Anim. 2009; 58(4):403-7. DOI: 10.1538/expanim.58.403. View

12.

van Noordwijk M, van Schaik C . The effects of dominance rank and group size on female lifetime reproductive success in wild long-tailed macaques,Macaca fascicularis. Primates. 2012; 40(1):105-30. DOI: 10.1007/BF02557705. View

13.

Mirsky M, Portugal S, Pisharath H, Osowski J, Kearney L . Utility of Orchidometric Parameters for Assessing Sexual Maturation in Male Cynomolgus Macaques (). Comp Med. 2017; 66(6):480-488. PMC: 5157964. View

14.

Buse E, Habermann G, Vogel F . Thymus development in Macaca fascicularis (Cynomolgus monkey): an approach for toxicology and embryology. J Mol Histol. 2006; 37(3-4):161-70. DOI: 10.1007/s10735-006-9057-2. View

15.

Sugimoto Y, Hanari K, Narita H, Honjo S . Normal hematologic values in the cynomolgus monkeys aged from 1 to 18 years. Jikken Dobutsu. 1986; 35(4):443-7. DOI: 10.1538/expanim1978.35.4_443. View

16.

Walthall K, Cappon G, Hurtt M, Zoetis T . Postnatal development of the gastrointestinal system: a species comparison. Birth Defects Res B Dev Reprod Toxicol. 2005; 74(2):132-56. DOI: 10.1002/bdrb.20040. View

17.

Snyder P, Everds N, Craven W, Werner J, Tannehill-Gregg S, Guzman R . Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis). Toxicol Pathol. 2016; 44(6):874-91. DOI: 10.1177/0192623316649258. View

18.

Vidal J, Bhaskaran M, Carsillo M, Denham S, Dubay O, Laing S . Spontaneous Findings in the Reproductive System of Sexually Mature Male Cynomolgus Macaques. Toxicol Pathol. 2022; 50(5):660-678. DOI: 10.1177/01926233221082302. View

19.

Liedigk R, Kolleck J, Boker K, Meijaard E, Md-Zain B, Abdul-Latiff M . Mitogenomic phylogeny of the common long-tailed macaque (Macaca fascicularis fascicularis). BMC Genomics. 2015; 16:222. PMC: 4371801. DOI: 10.1186/s12864-015-1437-0. View

20.

Chamanza R, Naylor S, Gregori M, Boyle M, Pereira Bacares M, Drevon-Gaillot E . The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (): A Contemporary Global and Multisite Review of Historical Control Data. Toxicol Pathol. 2022; 50(5):607-627. DOI: 10.1177/01926233221096424. View