Methods for the prediction of breeding success in male cynomolgus monkeys (Macaca fascicularis) used for reproductive toxicology studies.

The cynomolgus monkey (Macaca fascicularis) may be the species of choice for nonclinical reproductive toxicology studies because of the comparability of its reproductive processes to man, similarity of pharmacologic response to various test substances, and decreased probability of immunogenic response to biological therapeutic products. For success in conducting these studies, the male and female monkeys used need to be characterized thoroughly. This study focused on the evaluation of 42 male cynomolgus monkeys as potential breeders for reproductive toxicology studies. Parameters evaluated included age, body weight, testicular volume, serum testosterone levels, ejaculate volume, and sperm parameters (count, motility, and morphology). The results showed that physical parameters (age, body weight, testicular volume) were a good starting point for selection of potential breeder males. However, additional endpoints (testosterone; ejaculate volume; sperm count, motility and morphology; mating behavior) were also helpful as part of an overall "weight of evidence" approach to optimize selection of breeder males. In light of the data obtained in this study, 29 of 42 of the males evaluated were used with excellent success as breeder males for reproductive toxicology studies, resulting in an overall pregnancy rate of 36% when mated with sexually mature females. The successful breeder males were at least 6 y old, weighed at least 5 kg, had testicular volumes of at least 25 ml and serum testosterone levels of 1 to 10 ng/ml, and produced ejaculates with large numbers of sperm (median: 502 x 10(6) per ejaculate) of high quality (few morphologic defects and most sperm highly motile).