Characteristics of histologically confirmed endometriosis in cynomolgus monkeys

Abstract

STUDY QUESTIONWhat are the characteristics of spontaneous endometriosis in cynomolgus monkeys?SUMMARY ANSWERSpontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease.WHAT IS KNOWN ALREADYOne previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys.STUDY DESIGN, SIZE, DURATIONEndometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study.PARTICIPANTS/MATERIALS, SETTING, METHODSThe monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope.MAIN RESULTS AND THE ROLE OF CHANCEEndometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found.LIMITATIONS AND REASONS FOR CAUTIONSince laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed.WIDER IMPLICATIONS OF THE FINDINGSFurther investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology.STUDY FUNDING/COMPETING INTEREST(S)No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare.TRIAL REGISTRATION NUMBERN/A.

Spontaneous endometriosis in cynomolgus monkeys as a clinically relevant experimental model

“…Previously, we reported that a decrease in food consumption in the menstruation period was observed in monkeys with histologically confirmed endometriosis ( Nishimoto-Kakiuchi et al, 2016 ); therefore, we selected it as a candidate endometriosis-associated biological parameter. With this aim, we measured the food consumption of eight monkeys for 12 weeks and analyzed its correlation with the modified r-AFS score at the second laparoscopy ( Supplementary Fig.…”

“…Although the menstrual cycle of rhesus monkeys ( Macaca mulatta ) is seasonal, that of baboons ( Papio ) and cynomolgus monkeys ( Macaca fascicularis ) is similar to the human menstrual cycle (~4 weeks), so spontaneous endometriosis reported in cynomolgus monkeys ( Fanton and Hubbard, 1983 ; Ami et al, 1993 ) and baboons ( Merrill, 1968 ; D’Hooghe et al, 1991 ) is considered relevant. The histological characteristics have also been described fully and are considered to be clinically relevant in baboons ( D’Hooghe et al, 2009 ) and cynomolgus monkeys ( Nishimoto-Kakiuchi et al, 2016 ). Baboons are reportedly useful for endometriosis research because they are larger than cynomolgus monkeys, which makes it easier to observe the disease by laparoscopy and to obtain tissue samples.…”

“…Baboons are reportedly useful for endometriosis research because they are larger than cynomolgus monkeys, which makes it easier to observe the disease by laparoscopy and to obtain tissue samples. Conversely, being smaller in body size and a common laboratory animal, cynomolgus monkeys are easier to control in the laboratory setting ( Nishimoto-Kakiuchi et al, 2016 ; Yamanaka et al, 2012 ).…”

Animal models of endometriosis: Replicating the aetiology and symptoms of the human disorder

“…Menstruating primates can develop spontaneous disease although detection rates are generally reported as being low, in part because females are often only detected when the severity of their symptoms results in obvious changes in behaviour. Spontaneous disease with lesions resembling those in women was reported in cynomolgus monkeys in a large breeding facility in Japan (20,21). In these animals, symptoms included decreased food consumption (21); in a group of 27 retired breeders the majority had cystic lesions and co-incident adenomyosis was also detected (20).…”

“…Spontaneous disease with lesions resembling those in women was reported in cynomolgus monkeys in a large breeding facility in Japan (20,21). In these animals, symptoms included decreased food consumption (21); in a group of 27 retired breeders the majority had cystic lesions and co-incident adenomyosis was also detected (20). Dehoux et al studied 41 baboons at a Kenyan primate facility using laparoscopy to prospectively monitor them for 11 months (22).…”