Polyostotic fibrous dysplasia in a cynomolgus Macaque (Macaca fascicularis).

A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque.

Craniorachischisis and omphalocele in a stillborn cynomolgus monkey (Macaca fascicularis).

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities.

The baboon model (Papio hamadryas) of fetal loss: maternal weight, age, reproductive history and pregnancy outcome.

BACKGROUND: Several risk factors are associated with the incidence of human stillbirths. The prevention of stillbirths in women is a pressing clinical problem. METHODS: We reviewed 402 pathology records of fetal loss occurring in a large baboon (Papio spp.) colony during a 15-year period. Clinical histories of 565 female baboons with one or more fetal losses during a 20-year period were analyzed for weight, age, and reproductive history. RESULTS: Fetal loss was most common at term (35.57%) and preterm (28.61%) and less common in the first half of gestation (11.20%) and post-term (5.22%). Greater maternal weight, older age, history of stillbirth and higher parity were independent predictors for stillbirth. An exponential increase in the incidence of fetal loss was observed beginning at age 14 years in baboons. CONCLUSIONS: Fetal loss and maternal risk factors associated with stillbirths in baboons were similar to those documented in women.

Trisomy 17 in a baboon (Papio hamadryas) with polydactyly, patent foramen ovale and pyelectasis.

Trisomy 13 in humans is the third most common autosomal abnormality at birth, after trisomy 21 and trisomy 18. It has a reported incidence of between 1:5,000 and 1:30,000 live births. It is associated with multiple abnormalities, many of which shorten lifespan. We describe here the first reported case of a baboon (Papio hamadryas) with trisomy of chromosome 17, which is homologous to human chromosome 13. The trisomic infant was born to a consanguineous pair of baboons and had morphological characteristics similar to those observed in human trisomy 13, including bilateral polydactyly in the upper limbs, a patent foramen ovale, and pyelectasis. Molecular DNA analysis using human chromosome 13 markers was consistent with the affected infant inheriting two copies of chromosome 17 derived from the same parental chromosome. This trisomy was, therefore, due to either an error in meiosis II or the result of postzygotic nondisjunction. The parental origin, however, could not be determined.

Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta).

The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the most robust interventions for reducing the frequency of age-related diseases and for extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet well understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in a long-lived mammal. Male monkeys were begun on the diet in 1987, and females were added in 1992 to examine a possible difference in response to CR by sex. The CR monkeys have been maintained for over 10 years on a low-fat nutritional diet that provides a 30% calorie reduction compared to a control (CON) group. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, the rhesus monkey provides an excellent model for the effects of CR in humans. This study examined the effects of CR on chromosomal instability with aging. Significant age effects were found in both CR and CON groups for the number of cells with aneuploidy: old animals had a higher loss and a higher gain than young animals. However, there was no effect of age on chromosomal breakage or structural aberrations in either diet group. Diet had only one significant effect: the CR group had a higher frequency of chromatid gaps than did the CON group. CR, implemented in adult rhesus monkeys, does not have a major effect on the reduction of numerical or structural aberrations related to aging.

Primary amenorrhea associated with ovarian leiomyoma in a baboon (Papio hamadryas).

A 6-y-old female baboon was examined due to absence of menstrual cycling and secondary sex characteristics and failure to reproduce. The mammary glands and vaginal introitus were hypoplastic, the clitoris was prominent, and the perineal skin was immature with lack of cyclic color alterations and sexual swelling. Evaluation of the reproductive tract revealed a hypoplastic uterus and rudimentary ovaries with the presence of an ovarian leiomyoma within the right ovary. Hormonal values (estradiol, progesterone) were low and comparable to those of adult males or ovariectomized females. Adrenal and pituitary hormones (dehydroepiandrosterone, luteinizing and follicular stimulating hormones) and pituitary structure were within normal limits for this species. The baboon had a normal 42,XX karyotype. These findings suggest primary amenorrhea due to ovarian dysgenesis. This is the first report of a case of primary amenorrhea due to ovarian dysgenesis with a normal karyotype associated with a unilateral ovarian leiomyoma in the baboon. Continued studies of noncycling female nonhuman primates in captive breeding colonies may lead to a greater understanding of the underlying causes of this condition.

Spontaneous ovarian tumors in twelve baboons: a review of ovarian neoplasms in non-human primates.

Twelve spontaneous ovarian tumors were found in the Southwest Foundation for Biomedical Research baboon colony. These included four granulosa cell tumors, three teratomas, two endometrioid carcinomas, one seromucinous cystadenofibroma, a cystic papillary adenocarcinoma, and an ovarian carcinoma. Age was a pre-disposing factor. With one exception, the tumors of surface epithelial- and sex cordstromal origin occurred in baboons over 17 years of age. The exceptional animal was 7 years of age when a malignant granulosa cell tumor with Sertoli cell differentiation was identified. The two endometrioid tumors, which were found in 17- and 30-year-old animals, were both associated with endometriosis. In contrast, the teratomas, which are tumors of germ cell origin, were found in younger animals, i.e. 17 years of age or younger. One case of an ovarian carcinoma with metastases was observed in a 6-month-old infant. Cases of spontaneous ovarian tumors from the literature are reviewed.