Oral Squamous Cell Carcinoma in a Pigtailed Macaque (Macaca nemestrina)

An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque''s condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal–rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.Abbreviation: SCC, squamous cell carcinomaSquamous cell carcinomas (SCC) are one of the most commonly reported oral tumors. They are characterized as firm, nodular to irregular, soft-tissue masses that are often ulcerated.⁶ These tumors are frequently highly invasive to local bone and muscle and occasionally metastasize to local and regional lymph nodes.⁶ Histologically, SCC are characterized by keratin pearls, intercellular bridges, and positive cytokeratin staining on immunohistochemistry.^6,18 SCC have been associated with carcinogen exposure (such as bracken fern toxicosis in cattle), actinic radiation, and rarely with papillomatosis.⁸In general, neoplastic diseases are rare in nonhuman primates, and SCC and lymphoma are the 2 most commonly reported oral neoplasms in these species.³ SCC have most commonly been reported in rhesus macaques (Macaca mullata) and baboons (Papio spp.) among nonhuman primate species.⁹ In rhesus macaques, SCC has occurred in the oral cavity,⁹ integument,^9,22 esophagus,⁹ stomach,²¹ lung,^9,13 prepuce–penis,¹⁰ cervix,⁹ uterus,⁹ and eye.⁹ These neoplasms have also been reported to occur in cynomolgus macaques,^14,15,17,19 marmosets, squirrel monkeys, tree shrews, capuchins, tamarins, black spider monkeys, sooty mangabies, a spectacled langur, and an orangutan.⁹ No report describing SCC in a pig-tailed macaque has been published previously. The oral cavity is the most common site of SCC in nonhuman primates, and metastasis occurs in approximately 23% of cases.⁹ The average age at diagnosis of oral SCC in rhesus macaques is 17.6 y.²² In baboons, SCC is the third most common neoplasm, after intestinal adenocarcinoma and lymphosarcoma.⁴ The following case report describes an oral SCC in a pregnant pig-tailed macaque.     

Pneumatocele in a pig-tailed macaque (Macaca nemestrina)

Radiographic examination of a pig-tailed macaque (Macaca nemestrina) with pneumonia revealed a large pneumatocele. The pneumatocele, a thin-walled, partially fluid filled radiolucent area, occupied approximately one-third of the left thorax. Rapid resolution of the pneumatocele accompanied antimicrobial treatment of the pneumonia and coincided with clinical improvement. Severe pulmonary acariasis was found at postmortem 15 months later.     

In vitro fertilization in the pigtailed macaque (Macaca nemestrina)

The objective of this study was to investigate the possibility of collecting oocytes and semen from pigtailed macaques (Macaca nemestrina) and to establish a protocol for the production of viable embryos that would be suitable for transfer into surrogate females. A total of 82 oocytes were collected from a total of four females (on 2 d with two females each). Semen was collected from the same male on both occasions with respective ejaculate volumes of 0.55 and 0.1 mL containing 2 x 10(9) and 6.6 x 10(8)sperm/mL. Following insemination and after 48 h in culture, 42 (51.2%) of the oocytes had cleaved. Of these, 21 were selected based on developmental stage and their morphology and cryopreserved. The remainder was kept in culture for an additional 5 d, at which time three had reached the expanded blastocyst stage. A total of five transfers were performed with frozen-thawed embryos; two of these resulted in pregnancies and the birth of infants. The results of this study demonstrated that oocytes can be retrieved from pigtailed macaques and that such oocytes can be inseminated and cultured in vitro to the blastocyst stage and give rise to viable offspring after transfer into surrogate females.     

Supernumerary epiphyses in the macaque (Macaca nemestrina).

The frequency, age distribution and development of supernumerary epiphyses in the hand and foot were radiographically documented in 98 macaque fetuses and infants. Extra epiphyses were observed only on distal metacarpal 1 and metatarsal 1, and were present in 15% of a cross-sectional sample and 20% of a longitudinal sample. They appeared coincidentally with the ossification of other secondary epiphyses of the hand and foot. Development of extra epiphyses in this species seems to be a normal phenomenon.     

Detection of systemic amyloidosis in the pig-tailed macaque (Macaca nemestrina)

Secondary amyloidosis is a progressive systemic disease for which there is no reliable diagnostic assay, preventive measure, or treatment. In an attempt to elucidate an antemortem diagnosis, 30 female pig-tailed macaques (Macaca nemestrina) at the Washington National Primate Research Center were surveyed for amyloidosis. Amyloid was demonstrated histologically in 47% (14 of 30) of the animals. The distribution and severity of amyloid deposition was variable. Affected animals had a mean age (+/-1 standard deviation) of 13.2 +/- 4.9 y, which was significantly greater than the mean age of unaffected animals (9.3 +/- 4.1) y. Twelve tests were evaluated for detection of amyloidosis; the diagnostic value of each was determined through comparison of histologically positive and histologically negative animals. Diagnostic tests evaluated were endoscopic examination and biopsy of the stomach and colon, abdominal ultrasonography, hepatic radiology, serum amyloid A (SAA), endothelin 1, alpha-fetal protein, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyltransferase (GGT), alkaline phosphatase, cholesterol, blood urea nitrogen, total bilirubin, C-reactive proteins, and erythrocyte sedimentation rate. Amyloidotic animals demonstrated a distinctive serologic profile: elevated SAA, GGT, and AST in combination with decreased total protein and albumin. Radiology demonstrated hepatomegaly in animals with hepatic amyloid deposition. In the absence of known infection or trauma, an amyloidotic serologic profile and radiologic hepatomegaly are consistent with systemic amyloidosis in M. nemestrina.     

Heterochrony and sexual dimorphism in the pigtailed macaque (Macaca nemestrina)

Somatic growth is not a simple linear process with a constant rate of growth. The most successful attempts to quantify growth as a function of age or size have employed nonlinear techniques. Sexual dimorphism of primate growth, weight vs. age, was examined using nonlinear models with Sirianni and Swindler's ([1985] Growth and Development of the Pigtailed Macaque, Boca Raton, FL: CRC Press) growth data on the pigtailed macaque (Macaca nemestrina). The best fit of several exponential growth models was the Gompertz curve: Different multiple phase models were also fit, where each phase represents a distinct exponential component. The two-phase models proved to be the best (R² = .0.84 for females, 0.91 for males), suggesting that there are two growth spurts, one in infancy and one at puberty. The timing of the beginning and end of the first spurt is the same in males and females, but the rate, and value of the asymptote for this phase, is greater in males. The timing of the second spurt is earlier, and the rate of growth for this spurt is smaller in females than males. The sexual dimorphism in these species is not a simple rate change, but a complex interaction of timing and rate over the entire period of growth. It would be impossible to separate these entities with a linear, polynomial, or single-phase model of the data. While these data and results complement much of the existing work on adult dimorphism, they also emphasize the vital role that ontogenetic data have in elucidating the underlying evolutionary mechanisms that generate sexual dimorphism. © 1994 Wiley-Liss, Inc.     

Allogrooming in two species of macaque (Macaca nemestrina andMacaca radiata)

This paper analyzes allogrooming (social grooming) data collected from two large, fully integrated and long established social groups of macaques (one of pigtail macaques and one of bonnet macaques). The data demonstrates a species and sex difference for total allogrooming given with females of both species giving more grooming than the males and with pigtails as a species giving more grooming than bonnets. Also, pigtail females gave more allogrooming to clan members than to nonclan members, but this was not true for pigtail males, bonnet males, and bonnet females. Allogrooming given and allogrooming received by age class for both species showed development of a sexual dichotomy at three to four years. The analysis characterized some of the social structures extant in two closely related species of macaque, particularly the somewhat different use of allogrooming in pigtail females as opposed to the other three categories of animals. Social implications with relation to macaque societies are discussed.     

Intraspecific red cell enzyme variation in the pigtailed macaque (Macaca nemestrina)

The erythrocytes of 350 pigtailed macaques (Macaca nemestrina) were examined for electrophoretic variation of hemoglobin and 26 enzymes. Seven enzymes showed variation in more than 1% of individuals: phosphoglucose isomerase, phosphoglucomutase-1, soluble NADP-dependent isocitric dehydrogenase, peptidase A, peptidase C, 2,3-diphosphoglycerate mutase, and acid phosphatase. Variation with lesser frequency was found in soluble glutamic-oxalacetic transaminase, phosphoglycerate kinase, lactic dehydrogenase, and hemoglobin. Only eight samples were tested for esterase D, and one of these had a variant phenotype. Enzymes with no clear variation were adenylate kinase, adenosine deaminase, phosphofructokinase, hexokinase, pyruvate kinase, glyceraldehyde 3-phosphate dehydrogenase, aldolase, phosphoglycerate mutase, phosphopyruvate hydratase (enolase), phosphoglucomutase-3, and superoxide dismutase. There was father-to-son transmission of PGI, PGM-1, peptidase C, 6PGD, 2,3-DPGAM, NADP-ICD, and acid phosphatase variants, suggesting that these loci are autosomal as in man.     

Population Genetics of the Washington National Primate Research Center's (WaNPRC) Captive Pigtailed Macaque (Macaca nemestrina) Population

Pigtailed macaques (Macaca nemestrina) provide an important model for biomedical research on human disease and for studying the evolution of primate behavior. The genetic structure of captive populations of pigtailed macaques is not as well described as that of captive rhesus (M. mulatta) or cynomolgus (M. fascicularis) macaques. The Washington National Primate Research Center houses the largest captive colony of pigtailed macaques located in several different housing facilities. Based on genotypes of 18 microsatellite (short tandem repeat [STR]) loci, these pigtailed macaques are more genetically diverse than captive rhesus macaques and exhibit relatively low levels of inbreeding. Colony genetic management facilitates the maintenance of genetic variability without compromising production goals of a breeding facility. The periodic introduction of new founders from specific sources to separate housing facilities at different times influenced the colony's genetic structure over time and space markedly but did not alter its genetic diversity significantly. Changes in genetic structure over time were predominantly due to the inclusion of animals from the Yerkes National Primate Research Center in the original colony and after 2005. Strategies to equalize founder representation in the colony have maximized the representation of the founders’ genomes in the extant population. Were exchange of animals among the facilities increased, further differentiation could be avoided. The use of highly differentiated animals may confound interpretations of phenotypic differences due to the inflation of the genetic contribution to phenotypic variance of heritable traits. Am. J. Primatol. 74:1017‐1027, 2012. © 2012 Wiley Periodicals, Inc.     

Aggression in pigtailed macaque (Macaca nemestrina) breeding groups affects pregnancy outcome

Past research has shown that aggressive behaviors can affect female reproductive outcome in nonhuman primate captive breeding programs. In this study, aggressive behaviors were recorded in a colony of pigtailed macaque monkeys (Macaca nemestrina) and related to pregnancy outcome. For 22 weeks, behavioral data were collected from nine breeding groups, consisting of zero to one male (some males were removed after a cycle of conceptions for husbandry reasons) and four to eight females. Observations included all occurrences of 11 aggressive behaviors during 15 min observation sessions, 1-3 times a week. Mean weekly aggression levels during the study period were determined for each group as well as for each pregnancy. Aggression data were summarized with Principal Components Analyses. Results indicate that pigtailed macaque aggression falls into five distinctive categories: warn, engage, threaten, pursue, and attack. Breeding groups differed in their levels of aggression, even after controlling for group size, presence of a sire, and group stability. Levels of the five aggression categories were found to affect the probability that a pregnancy ended in either a natural birth of a live infant, a clinical intervention producing a live infant, or a nonviable outcome. The predictive value of aggression was significant when clinical interventions were included as possible reproductive outcomes. Behavioral observation of captive groups could identify "risk" conditions affecting pregnancy outcome and the requirement for clinical intervention.     

Phylogeographic analysis of pigtail macaque populations (Macaca nemestrina) inferred from mitochondrial DNA

Mitochondrial DNA variation was surveyed in nine populations of the pigtail macaque (Macaca nemestrina), covering all three recognized subspecies in Southeast Asia. To do this, a 2,300 base pair fragment spanning the mitochondrial NAD 3 and NAD 4 genes and flanking tRNA subunits leucine and glycine was targeted for amplification and digested with a battery of 16 restriction endonucleases. Out of a total of 107 individuals, 32 unique haplotypes could be distinguished. Parsimony and neighbor-joining analyses grouped the haplotypes into five strongly supported assemblages representing China/Thailand, Malaysia, Sumatra, Borneo, and Siberut. These results indicate that the mainland and island mtDNA haplotypes are strictly and uniquely limited to the geographic ranges of the recognized morphological subspecies. Cladistic and neighbor-joining analyses indicate that inferred phylogenies of mtDNA haplotypes are congruent with subspecies designations. Furthermore, in support of morphological studies, results indicate that the Mentawai macaque is most likely not a distinct species but a subspecies of M. nemestrina. Am J Phys Anthropol 104:35–45, 1997. © 1997 Wiley-Liss, Inc.     

Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol

Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.     

Simian Varicella Virus in Pigtailed Macaques (Macaca nemestrina): Clinical, Pathologic, and Virologic Features

Simian varicella virus (SVV; Cercopithecine herpesvirus 9) is a naturally occurring herpesvirus of nonhuman primates. Here we present the clinical, pathologic, and virologic findings from 2 cases of SVV in adult female pigtailed macaques (Macaca nemestrina). The initial case presented with hyperthermia and a diffuse inguinal rash which spread centripetally, progressing to vesiculoulcerative dermatitis of the trunk, face, and extremities. At 96 h after presentation, the animal was anorexic and lethargic and had oral and glossal ulcerations. Euthanasia was elected in light of the macaque''s failure to respond to clinical treatment. Seven days after the first case was identified, a second macaque presented with a vesicular rash and was euthanized. Gross necropsy lesions for both cases included vesicular, ulcerative dermatitis with mucocutaneous extension and hepatic necrosis; the initial case also demonstrated necrohemorrhagic gastroenterocolitis and multifocal splenic necrosis. Histology confirmed herpetic viral infection with abundant intranuclear inclusion bodies. Immunofluorescence assays detected antibodies specific for SVV. PCR assays of vesicular fluid, tissue, and blood confirmed SVV and excluded varicella–zoster virus (Human herpesvirus 3). Serology for Macacine herpesvirus 1 (formerly Cercopithecine herpesvirus 1), poxvirus (monkeypox), and rubella was negative. Banked serum samples confirmed SVV exposure and seroconversion. Investigation into the epidemiology of the seroconversion demonstrated a SVV colony prevalence of 20%. The described cases occurred in animals with reconstituted immune systems (after total-body irradiation) and demonstrate the clinical effects of infection with an endemic infectious agent in animals with a questionable immune status.Abbreviations: IFA, immunofluorescence assay; SVV, simian varicella virus; TBI, total body irradiation; WaNPRC, Washington National Primate Research Center; VZV, varicella–zoster virus; McHv1, Macacine herpesvuris 1; SRV-2, Simian retrovirus 2 (type D)Simian varicella virus (SVV; Cercopithecine herpesvirus 9) is a naturally occurring herpesvirus of Old World primates responsible for sporadic epizootics in biomedical research facilities.² Signs of infection include fever, vesicular skin lesions, hemorrhagic ulceration throughout the gastrointestinal tract, and multifocal hemorrhagic necrosis of the liver, spleen, lymph nodes, and endocrine organs.^6,7,8 Other names for SVV include Delta herpesvirus, Liverpool vervet virus, patas herpesvirus, and Medical Lake macaque virus.^{16, 20-23} Like many other herpesviruses, SVV establishes persistent lifelong infections, with viral DNA detectable in neural ganglia.¹² Infection with SVV does not necessarily lead to lifelong latency, and periodic reactivation of SVV may occur.³ SVV is genetically and antigenically similar to Human herpesvirus 3,² commonly known as varicela–zoster virus (VZV), the etiologic agent of chickenpox and shingles in humans. SVV in macaques and VZV in man present with similar clinical signs; SVV has been proposed as an animal model of VZV disease in man.²⁴ Rarely, VZV may occur in higher primates (Gorilla).¹⁸ The 2 viruses must be distinguished from one another through molecular techniques.^1,410,11 Both viral infections are usually mild and self-limiting in immunocompetent hosts,^4,8 reactivation and viral shedding may occur during times of stress or immunosupression.^80,21,22A recent review of SVV in Old World Monkeys⁸ focused on SVV as a disease of nonhuman primates. This case report expands on the 2 most recent cases of SVV mentioned in that review.⁸ The animals described were housed in accordance with the regulations of the Animal Welfare Act and the recommendations of the Guide for the Care and Use of Laboratory Animals¹¹ at the Washington National Primate Research Center (WaNPRC) facility in Seattle. The Institutional Animal Care and Use Committee of the University of Washington approved all aspects of the study to which the animals were assigned. The 2 clinical cases described in this report originated at the WaNPR–Seattle facility; contact animals described originated at the WaNPR–Tulane facility. When animals are relocated between the 2 facilities, they are processed through a domestic quarantine consisting of isolation for 30 d, during which time 3 tuberculin skin tests, 2 physical examinations, and 1 complete blood count and serological panel are performed. The WaNPRC–Tulane facility houses a breeding colony founded by animals relocated to Louisiana from the WaNPRC–Medical Lake facility in 1996.     

Intra-amniotic inoculation of pigtailed macaque (Macaca nemestrina) fetuses with SIV and HIV-1

Six pregnant pigtailed macaques (Macaca nemestrina) were inoculated intra-amniotically (i.a.) with SIV_Mne. All became viremic and seroconverted; three viable offspring were SIV-positive and at autopsy showed disseminated viral infection; one of three abortuses had SIV-infected thymic macrophages. Three of five pregnant macaques inoculated i.v. and/or i.a. with HIV-1_LAI became virus-positive, and four seroconverted, suggesting fetal-maternal transmission. One abortus had HIV-1-antigen in lymph nodes and brain; one infant, culture-positive at birth, died at age 11 days of disseminated HIV-1 infection.     

A periodic dosing model of fetal alcohol syndrome in the pig-tailed macaque (Macaca nemestrina)

A nonhuman primate on a periodic ethanol dosing schedule should provide a model of fetal alcohol syndrome (FAS) most relevant to the majority of pregnant women who are “social drinkers” and can exercise reasonable control over their ethanol intake. In this pilot study, four pregnant pig-tailed macaques (Macaca nemestrina) received ethanol once a week from 40 days' gestation. Doses were 2.5 gm/kg for three moderate-dose animals (MDAs) and 4.1 gm/kg for one high-dose animal (HDA). Peak blood ethanol levels reached a mean of 240–256 mg/dl for the MDAs and averaged 379 mg/dl for the HDA. Peak acetaldehyde did not vary with dose. One MDA aborted after the first dose. The other three pregnancies were compared with eight to ten control pregnancies, and the infants' development over the first six months was compared with that of the control offspring. Nutritional status of the pregnant females was normal. The fetal heart rate response to maternal restraint was absent in the HDA. Gestational duration and simian Apgar scores were normal. All three infants were abnormally large, and two were also abnormally heavy, with body weight appropriate to skeletal size. Skeletal maturation, judged by ossification and tooth eruption, was not accelerated. The high-dose infant (HDI) was scaphocephalic, with an underdeveloped cranial base and midface, and its brain was small and dysplastic; its reflex, motor, and cognitive development were retarded. One moderate-dose infant (MDI) had some brain abnormalities; it was hyperkinetic and showed developmental retardation on several behavioral measures. The other MDI was normal. We conclude that the periodic model offers an effective means of investigating FAS in M. nemestrina. Furthermore, when nutrition is maintained, intermittent intake of ethanol by the pregnant primate does not necessarily reatard fetal growth.     

The skin of primates. XXXVII. The skin of the pig-tail macaque (Macaca nemestrina)

The skin of the pig-tail macaque is basically similar to that of the rhesus monkey and the stump-tail macaque. The epidermis is thin and contains occasional basal melanocytes. The dermis, rich in elastic fibers, is practically free of pigment-containing cells. The upper dermis is highly vascular in the perianal region and sex skin. Cholinesterase-reactive nerve endings are plentiful beneath the friction surfaces of the pes and manus, mucous membranes, and junction of the hairy gluteus and glabrous ischial callosity. Hederiform-like endings are present in the eyelid, pinna, and frontal scalp. Apocrine and eccrine sweat glands occur throughout the hairy skin in a 2–3: 1 ratio. Both types are invested by nerves reactive for acetyl- and butyrylcholinesterase.     

Correlation of perineal detumescence and ovulation in the pigtail macaque (Macaca nemestrina).

A study was made of the relationship between ovulation and perineal detumescence in the pigtail macaque (Macaca nemestrina). Daily laparoscopic examation of both ovaries was made beginning on the 9th day of the menstrual cycle. The appearance of the ovaries was recorded and photographs were taken of the perineum and ovaries. This procedure was repeated daily until the 5th day after ovulation or until the 20th day of the menstrual cycle for presumed anovulatory cycles. The time at which ovulation occurred was correlated with first signs of detumescence, both events occurring within a 24-hour period.     

Infant abuse associated with psychosocial stress in a group-living pigtail macaque ( Macaca nemestrina) Mother

This study reports a case of infant abuse by a pigtail macaque mother living in a captive social group. Patterns of abusive behavior appeared three weeks after the birth of the infant and were in strict temporal as sociation with the repeated kidnapping and severe harassment of the infant by the alpha-female in the group. Before and after the period of social stress, the mother exhibited proper caregiving behavior towards her infant. The analysis of the abusive mother's style of interaction with her infant relative to three control mothers indicated that she was an extremely permissive mother. It is argued that the mother's failure to adapt her mothering style to better protect her infant during the period of repeated kidnappings and the resulting lack of control over the situation may be the mechanism by which stress precipitated infant abuse. © 1994 Wiley-Liss, Inc.     

Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina)

Ethanol was orally administered once per week to gravid pig-tailed macaques (Macaca nemestrina) in doses of 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg. A control group received a sucrose solution, isocaloric and isovolemic to the highest ethanol dose. Pregnancy was followed after 116 possible conceptions in 54 females. Peak plasma ethanol concentrations (PPECs) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. An increased rate of spontaneous abortion was related to ethanol exposure at and above 1.8 g/kg (mean PPEC = 205 mg/dl). Pregnancy failure in the first 30 days of gestation increased at doses above 2.5 g/kg. The effect on pregnancy outcome of weekly exposure to ethanol in this nonhuman primate is comparable to available data on humans. The methodology of this study represents an effective model for studying ethanol teratogenesis in a nonhuman primate.