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Toxicologic Pathology
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Articles

Physiology and Endocrinology of the Ovarian Cycle in Macaques

Gerhard F. Weinbauer1
Marc Niehoff1
Michael Niehaus1
Shiela Srivastav1
Antje Fuchs1
Eric Van Esch2
J. Mark Cline3

1 Covance Laboratories GmbH, Muenster, Germany
2 Schering-Plough Corporation, the Netherlands
3 Wake Forest University, School of Medicine, Winston-Salem, North Carolina, USA

Correspondence: Prof. Dr. Gerhard F. Weinbauer, Director Research and Safety Assessment, Covance Laboratories GmbH, Kesselfeld 29, D-48163 Muenster, Germany; Phone: +49 251 97980; fax: +49 251 784697.

Macaques provide excellent models for preclinical testing and safety assessment of female reproductive toxicants. Currently, cynomolgus monkeys are the predominant species for (reproductive) toxicity testing. Marmosets and rhesus monkeys are being used occasionally. The authors provide a brief review on physiology and endocrinology of the cynomolgus monkey ovarian cycle, practical guidance on assessment and monitoring of ovarian cyclicity, and new data on effects of social housing on ovarian cyclicity in toxicological studies. In macaques, cycle monitoring is achieved using daily vaginal smears for menstruation combined with cycle-timed frequent sampling for steroid and peptide hormone analysis. Owing to requirements of frequent and timed blood sampling, it is not recommended to incorporate these special evaluations into a general toxicity study design. Marmosets lack external signs of ovarian cyclicity, and cycle monitoring is done by regular determinations of progesterone. Cynomolgus and marmoset monkeys do not exhibit seasonal variations in ovarian activity, whereas such annual rhythm is pronounced in rhesus monkeys. Studies on pair- and group-housed cynomolgus monkeys revealed transient alterations in the duration and endocrinology of the ovarian cycle followed by return to normal cyclicity after approximately six months. This effect is avoided if the animals had contact with each other prior to mingling. These experiments also demonstrated that synchronization of ovarian cycles did not occur.

Competing Interests: This article was sponsored by Covance Inc. and Schering-Plough. Gerhard F. Weinbauer, Marc Niehofg, Michael Niehaus, Shiela Srivasav, and Antje Fuchs are employed by Covance Inc. Eric Van Esch is employed by Schering-Plough. No other competing interests were declared.

Key Words: cynomolgus monkey • rhesus monkey • marmoset • reproduction • female

Abbreviations: GnRH, gonadotropin-releasing hormone • LH, luteinizing hormone • FSH, follicle-stimulating hormone • AN, arcuate nucleus

Toxicologic Pathology, Vol. 36, No. 7 Suppl, 7S-23S (2008)
DOI: 10.1177/0192623308327412


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Toxicol PatholHome page
E. van Esch, J. M. Cline, E. Buse, and G. F. Weinbauer
The Macaque Endometrium, with Special Reference to the Cynomolgus Monkey (Macaca fascicularis)
Toxicol Pathol, December 1, 2008; 36(7_suppl): 67S - 100S.
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