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PubMed1993

Mhc-DRB and -DQA1 nucleotide sequences of three lowland gorillas. Implications for the evolution of primate Mhc class II haplotypes.

Mhc-DRB and -DQA1 second-exon and -DRB 3'-untranslated-region nucleotide sequences of three lowland gorillas with no known family relationship with each other and of two HLA homozygous typing cell lines were determined and compared with published primate Mhc-DRB and -DQA1 sequences. Eleven distinct MhcGogo-DRB second-exon sequences were found, which represent the gorilla counterparts of the HLA-DRB1*03, -DRB1*10, -DRB3, -DRB5, and -DRB6 allelic lineages. One Gogo-DRB second-exon sequence does not have an obvious human counterpart and is tentatively designated Gogo-DRBY*01. The gorilla equivalents of the HLA-DRB2 and -DRB8 loci were identified as judged on Mhc-DRB 3'-untranslated-region sequences. In addition, four different Gogo-DQA1 alleles belonging to three different allelic lineages were detected. The Mhc-DRB-DQA1 haplotypes of these gorillas were deduced based on the obtained Mhc-DRB and -DQA1 sequences and the two published Mhc-DRB haplotypes of the lowland gorilla Sylvia. All deduced Gogo-DRB-DQA1 haplotypes show gene constellations different from known HLA-DRB-DQA1 haplotypes, while some of the Gogo-DRB haplotypes presented here contain more DRB genes than the HLA-DRB haplotypes. Based on phylogenetic trees, bootstrap analyses, and the gorilla, chimpanzee, and human Mhc-DRB haplotypes described, we propose that at least two Mhc-DRB loci, here tentatively designated Mhc-DRBI and -DRBII, existed on an ancient primate Mhc-DRB haplotype. The Mhc-DRB1*01, -DRB1*02 (-DRB1*15 and -DRB1*16), -DRB1*03 (-DRB1*03, -DRB1*08, -DRB1*11, -DRB1*12, -DRB1*13, and DRB1*14), and -DRB1*10 allelic lineages and -DRB3 and -DRBY loci probably evolved from the hypothetical primate Mhc-DRBI locus, whereas the present primate Mhc-DRB2, -DRB4, and -DRB6 loci originate from the ancient Mhc-DRBII locus of this core primate Mhc-DRB haplotype.

Amino Acid Sequence↗
PubMed1993

Qualitative and quantitative studies of cytokines synthesized and secreted by non-human primate peripheral blood mononuclear cells.

Non-human primates are being utilized in a variety of pre-clinical studies, including those involved with mechanisms of organ transplant rejection and those being used as models to test the efficacy of vaccines against a variety of infectious diseases, most notably AIDS. These studies clearly involve immunological effector mechanisms, which include the interaction between T cells, B cells, monocytes, and cytokines that regulate these interactions. However, there is very little known about assays and quantitation of cytokines from non-human primates. In attempts to address this issue, bioassays, commercially available EIA kits, and primer pairs and probes specific for human cytokines were evaluated for their ability to detect and quantitate the non-human primate homologues. Data suggest that although the EIA kits that were evaluated for human IL-1 alpha, IFN-gamma, and TNF-beta failed, the EIA kits for IL-1 beta, IL-2, IL-4, IL-6, and TNF-alpha, the bioassays and RT-PCR assays for each of the cytokines were successful in detection and most likely quantitation of the non-human primate cytokine homologues. These assays will greatly facilitate future studies on the role of cytokines in these non-human primate studies.

Animals↗
PubMed2005

Molar scaling in strepsirrhine primates.

We examined how maxillary molar dimensions change with body and skull size estimates among 54 species of living and subfossil strepsirrhine primates. Strepsirrhine maxillary molar areas tend to scale with negative allometry, or possibly isometry, relative to body mass. This observation supports several previous scaling analyses showing that primate molar areas scale at or slightly below geometric similarity relative to body mass. Strepsirrhine molar areas do not change relative to body mass(0.75), as predicted by the metabolic scaling hypothesis. Relative to basicranial length, maxillary molar areas tend to scale with positive allometry. Previous claims that primate molar areas scale with positive allometry relative to body mass appear to rest on the incorrect assumption that skull dimensions scale isometrically with body mass. We identified specific factors that help us to better understand these observed scaling patterns. Lorisiform and lemuriform maxillary molar scaling patterns did not differ significantly, suggesting that the two infraorders had little independent influence on strepsirrhine scaling patterns. Contrary to many previous studies of primate dental allometry, we found little evidence for significant differences in molar area scaling patterns among frugivorous, folivorous, and insectivorous groups. We were able to distinguish folivorous species from frugivorous and insectivorous taxa by comparing M1 lengths and widths. Folivores tend to have a mesiodistally elongated M1 for a given buccolingual M1 width when compared to the other two dietary groups. It has recently been shown that brain mass has a strong influence on primate dental eruption rates. We extended this comparison to relative maxillary molar sizes, but found that brain mass appears to have little influence on the size of strepsirrhine molars. Alternatively, we observed a strong correlation between the relative size of the facial skull and relative molar areas among strepsirrhines. We hypothesize that this association may be underlain by a partial sharing of the patterning of development between molar and facial skull elements.

Animals↗
PubMed2006

Application of microarray technology in primate behavioral neuroscience research.

Gene expression profiling of brain tissue samples applied to DNA microarrays promises to provide novel insights into the neurobiological bases of primate behavior. The strength of the microarray technology lies in the ability to simultaneously measure the expression levels of all genes in defined brain regions that are known to mediate behavior. The application of microarrays presents, however, various limitations and challenges for primate neuroscience research. Low RNA abundance, modest changes in gene expression, heterogeneous distribution of mRNA among cell subpopulations, and individual differences in behavior all mandate great care in the collection, processing, and analysis of brain tissue. A unique problem for nonhuman primate research is the limited availability of species-specific arrays. Arrays designed for humans are often used, but expression level differences are inevitably confounded by gene sequence differences in all cross-species array applications. Tools to deal with this problem are currently being developed. Here we review these methodological issues, and provide examples from our experiences using human arrays to examine brain tissue samples from squirrel monkeys. Until species-specific microarrays become more widely available, great caution must be taken in the assessment and interpretation of microarray data from nonhuman primates. Nevertheless, the application of human microarrays in nonhuman primate neuroscience research recovers useful information from thousands of genes, and represents an important new strategy for understanding the molecular complexity of behavior and mental health.

Animals↗
PubMed1998

Helminth and protozoan gastrointestinal tract parasites in captive and wild-trapped African non-human primates.

The objective of this study was to investigate the gastro-intestinal (GIT) parasites commonly occurring in captive and wild-trapped (WT) non-human primates (baboons, vervets and Sykes) in Kenya and compare their prevalence. Three hundred and fifteen faecal samples were subjected to a battery of diagnostic tests, namely, direct smear, modified formal ether sedimentation, Kato thick smear, Harada-Mori techniques for parasite detection and culture to facilitate nematode larvae identification. Of these, 203 (64.4%) harboured helminths and 54 (17.1%) had protozoa. The helminth parasites comprised Strongyloides fulleborni 141 (44.8%), Trichuris trichuira 200 (63.5,%), Oesophagostomum sp. 48 (15.2%), Trichostrongylus sp. 73 (23.2%), Enterobius vermicularis 44 (14.0%), Schistosoma mansoni 4/92 (4.3%) and Streptopharagus sp. 68 (21.6%). Protozoan parasites consisted of Entamoeba coli 204 (64.8%), Balantidium coli 127 (40.3%) and Entamoeba histolytica 78 (24.8%). Both WT and colony-borne (CB) primates had similar species of parasites, but higher prevalences of protozoan infection were observed in CB baboons while helminth infections were relatively more common in WT primates. Some of the parasites observed in this study are reported to be zoonotic in various parasitological literatures. Chemoprophylaxis and other managerial practices were believed to be responsible for the lower worm prevalence in CB primates. Similar intervention against protozoa and other agents will not only improve primate health, but also increase safety to animal handlers and colony workers.

Animals↗
PubMed2002

Fluid distribution measurement between body compartments in primates in disclosing fluid retention during prolonged hypokinesia.

Body fluid homeostasis undergoes significant changes during hypokinesia (diminished movement). Understanding of fluid transfer between body fluid compartments and its regulating mechanisms was the aim of this study for disclosing impaired fluid retention during hypokinesia (HK). Studies were done on 12 male Macaca mulatta (rhesus monkeys) aged three to five years (5.15 to 6.56 kg) during 90 days period of pre-HK and 90 days period of HK. All primates were divided equally into two groups: vivarium control primates (VCP) and hypokinetic primates (HKP). Hypokinetic primates were kept for 90 days in small individual cages that restricted their movements in all directions without hindering food and fluid intakes. Control primates were housed in individual cages without their movements being restricted. Total body fluid (TBF), intracellular fluid volume (IFV) and circulating plasma volume (CPV) decreased significantly (p < 0.05), while extracellular fluid volume (EFV) and interstitial fluid volume (IsFV) decreased significantly (p < 0.05) at the initial seven days of the HK period and after the 7th day increase progressively in HKP compared with their pre-HK values and their respective control values in VCP. Fluid excretion, urinary and plasma sodium (Na) and potassium (K) levels increased significantly (p < 0.05), while fluid intake and fluid retention decreased significantly (p < 0.05) in HKP compared with their pre-HK values and their respective controls in VCP. The measured parameters did not change in VCP compared with their pre-HK values. It was concluded that decreased IFV and CPV may demonstrate fluid depletion, while marked increase of fluid loss despite of fluid depletion may demonstrate impair fluid retention during HK. Dissociation between fluid loss and fluid depletion may demonstrate the presence of reduced fluid retention as the mechanism of development of fluid depletion during HK.

Animals↗
PubMed2000

Gingival crevicular fluid inflammatory mediators and bacteriology of gingivitis in nonhuman primates related to susceptibility to periodontitis.

The hypothesis to be tested was that the microbiota and resulting local host inflammatory response characteristics in oral conditions of high levels of chronic gingival inflammation increases susceptibility to progressing periodontitis. This study used cynomolgus monkeys, Macaca fascicularis (nonhuman primates), with high and low levels of long-standing gingival inflammation to define the profiles of gingival crevicular fluid mediators, cytokines and immunoglobulins; describe the subgingival microbiota; and evaluate their susceptibility to ligature-induced periodontitis. Sixteen nonhuman primates were stratified into two groups (HI, LO) based upon Bleeding Index as a measure of the natural level of inflammation (HI = 1.26 +/- 0.45; LO = 0.22 +/- 0.16). The host mediator levels, subgingival microbiota, and clinical characteristics of the LO and HI groups were compared after 30 days of oral hygiene, during a 30 day experimental gingivitis (7, 14, and 30 days), and during periodontitis (30, 60, and 90 days). The results demonstrated that nonhuman primates with high levels of long-standing gingival inflammation when compared to those nonhuman primates with low inflammation show: 1) different inflammatory mediator profiles in gingival crevicular fluid (particularly for immunoglobulin A (IgA) and IgG levels), 2) a different quantitative and qualitative subgingival microbiota; and 3) a similar progression of periodontitis. Thus, while variations in host inflammatory responses to local factors exist in the nonhuman primates, an extensive subgingival challenge (such as ligation) may negate these individual differences.

Animals↗
PubMed2003

Immune parameters relevant to neural xenograft survival in the primate brain.

The lack of supply and access to human tissue has prompted the development of xenotransplantation as a potential clinical modality for neural cell transplantation. The goal of the present study was to achieve a better understanding of the immune factors involved in neural xenograft rejection in primates. Initially, we quantified complement mediated cell lysis of porcine fetal neurons by primate serum and demonstrated that anti-C5 antibody treatment inhibited cell death. We then developed an immunosuppression protocol that included in vivo anti-C5 monoclonal antibody treatment, triple drug therapy (cyclosporine, methylprednisolone, azathioprine) and donor tissue derived from CD59 or H-transferase transgenic pigs and applied it to pig-to-primate neural cell transplant models. Pre-formed alphaGal, induced alphaGal and primate anti-mouse antibody (PAMA) titers were monitored to assess the immune response. Four primates were transplanted. The three CD59 neural cell recipients showed an induced anti-alphaGal response, whereas the H-transferase neural cell recipient exhibited consistently low anti-alphaGal titers. Two of these recipients contained surviving grafts as detected by immunohistochemistry using selected neural markers. Graft survival correlated with high dose cyclosporine treatment, complete complement blockade and the absence of an induced PAMA response to the murine anti-C5 monoclonal antibodies.

Animals↗
PubMed2004

Amino acid domains control the circulatory residence time of primate acetylcholinesterases in rhesus macaques (Macaca mulatta).

An array of 13 biochemically well defined molecular forms of bovine, human and newly cloned rhesus macaque (Macaca mulatta) AChEs (acetylcholinesterases) differing in glycosylation and subunit assembly status were subjected to comparative pharmacokinetic studies in mice and rhesus macaques. The circulatory lifetimes of recombinant bovine, macaque and human AChEs in mice were governed by previously determined hierarchical rules; the longest circulatory residence time was obtained when AChE was fully sialylated and tetramerized [Kronman, Chitlaru, Elhanany, Velan and Shafferman (2000) J. Biol. Chem. 275, 29488-29502; Chitlaru, Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613-625]. In rhesus macaques, bovine molecular forms still obeyed the same hierarchical rules, whereas primate AChEs showed significant deviation from this behaviour. Residence times of human and rhesus AChEs were effectively extended by extensive sialylation, but subunit tetramerization and N-glycan addition had a marginal effect on their circulatory longevity in macaques. It appears that the major factor responsible for the differential pharmacokinetics of bovine and primate AChEs in macaques is related to differences in primary structure, suggesting the existence of a specific mechanism for the circulatory clearance of primate AChEs in rhesus macaques. The 35 amino acids that differ between bovine and primate AChEs are clustered within three defined domains, all located at the enzyme surface, and may therefore mediate the facilitated removal of primate cholinesterases specifically from the circulation of monkeys. These surface domains can be effectively masked by poly(ethylene glycol) appendage, resulting in the generation of chemically modified human and macaque AChEs that reside in the circulation for extraordinarily long periods of time (mean residence time of 10000 min). This extended residence time is similar to that displayed by native macaque butyrylcholinesterase (9950 min), which is the prevalent cholinesterase form in the circulation of adult macaques.

Acetylcholinesterase↗
PubMed1985

A primate model (Macaca mulatta) to study the pharmacokinetics of heparin and its fractions.

We have extensively studied the hemostatic parameters and the responses to the anticoagulant action of heparin and its fractions in the primate model (M. mulatta) and found these to be identical to those obtained in humans. The functional properties of antithrombin III, alpha 2-antiplasmin, and platelet factor 4 were also identical to humans in amidolytic and coagulant assays. Human antibodies against FPA, B beta 15-42 peptide, platelet factor 4, and thromboxane B2 reacted with the primate antigen, and assays were developed to measure these parameters in primates. Infusion of activated prothrombin complex concentrates (more than 100 U/kg/day) on a continual basis up to 3 days resulted in a hypercoagulable state manifested by an elevation of FPA, thromboxane B2, and changes in the thrombelastographic patterns. Similarly, infusion of homologous primate serum also resulted in a hypercoagulable state, as was evident by a sharp increase in the FPA levels. The antithrombotic effects of intravenous and subcutaneous administration of heparin, its low molecular fraction, and their constituents were studied after intravenous and subcutaneous injections. The low molecular weight fractions showed the most effective antithrombotic effects, whereas somewhat milder protection was observed with the starting material and highly anionic fraction. The prolongation of global tests, such as the APTT, TT, and changes in the thromboelastogram did not correlate with the reduction in the blood markers of hypercoagulable state. A modified simplate bleeding time method was used to study the effect of heparin and its fractions on the bleeding profile of heparin fractions. The components of fibrinolytic systems were also measurable in both the clot-based and amidolytic methods to predict the profibrinolytic actions of heparin fractions in its mode. These studies suggest that plasma markers, such as the platelet release proteins, products of thrombin activation, and prostaglandin metabolites, may provide better indices in the monitoring of the antithrombotic actions of newer heparins and antithrombotic drugs. Studies suggest that the pathophysiologic responses after a thrombogenic trigger in the primate model are close to humans, and drug modulation of these may provide relevant clinical information. This model provides the most similar preclinical model to study the actions of heparin fractions.

Animals↗
PubMed1989

The role of propulsive muscles of the shoulder during quadrupedalism in vervet monkeys (Cercopithecus aethiops): implications for neural control of locomotion in primates.

In comparative anatomical studies of the shoulder, the humeral retractors are often grouped together as propulsive muscles, which are important in the propulsive stroke of the forelimb during quadrupedal locomotion. Electromyographic (EMG) analyses of these muscles in opossums, cats, and dogs in general have confirmed such conclusions. An EMG study of chimpanzee shoulder muscles during knuckle-walking found, however, that the humeral retractors are either inactive or perform a function unrelated to propulsion (Larson & Stern, 1987). This contrast in muscle recruitment patterns between chimpanzees and more "typical" mammalian quadrupeds was attributed to the derived morphology of the chimpanzee shoulder. The present study examines the activity patterns of the humeral retractors in the vervet monkey, a primate more closely resembling nonprimate mammals in its shoulder morphology. The results of this EMG analysis show that despite the significant differences in anatomy between chimpanzees and vervets, the two species display very similar muscle recruitment patterns during quadrupedalism, and there is evidence for this same pattern in other species of primates. These differences in muscle activity patterns between primates and nonprimate mammals may be related to changes in the neurological control of locomotion in primates due to the evolutionary development of manipulative abilities in the primate forelimb.

Journal Article↗
PubMed2006

Arrival and diversification of caviomorph rodents and platyrrhine primates in South America.

Platyrrhine primates and caviomorph rodents are clades of mammals that colonized South America during its period of isolation from the other continents, between 100 and 3 million years ago (Mya). Until now, no molecular study investigated the timing of the South American colonization by these two lineages with the same molecular data set. Using sequences from three nuclear genes (ADRA2B, vWF, and IRBP, both separate and combined) from 60 species, and eight fossil calibration constraints, we estimated the times of origin and diversification of platyrrhines and caviomorphs via a Bayesian relaxed molecular clock approach. To account for the possible effect of an accelerated rate of evolution of the IRBP gene along the branch leading to the anthropoids, we performed the datings with and without IRBP (3768 sites and 2469 sites, respectively). The time window for the colonization of South America by primates and by rodents is demarcated by the dates of origin (upper bound) and radiation (lower bound) of platyrrhines and caviomorphs. According to this approach, platyrrhine primates colonized South America between 37.0 +/- 3.0 Mya (or 38.9 +/- 4.0 Mya without IRBP) and 16.8 +/- 2.3 (or 20.1 +/- 3.3) Mya, and caviomorph rodents between 45.4 +/- 4.1 (or 43.7 +/- 4.8) Mya and 36.7 +/- 3.7 (or 35.8 +/- 4.3) Mya. Considering both the fossil record and these molecular datings, the favored scenarios are a trans-Atlantic migration of primates from Africa at the end of the Eocene or beginning of the Oligocene, and a colonization of South America by rodents during the Middle or Late Eocene. Based on our nuclear DNA data, we cannot rule out the possibility of a concomitant arrival of primates and rodents in South America. The caviomorphs radiated soon after their arrival, before the Oligocene glaciations, and these early caviomorph lineages persisted until the present. By contrast, few platyrrhine fossils are known in the Oligocene, and the present-day taxa are the result of a quite recent, Early Miocene diversification.

Animal Migration↗
PubMed1997

Molecular cloning and gene expression analysis of PSP94 (prostate secretory protein of 94 amino acids) in primates.

Prostate secretory protein of 94 amino acids (PSP94) has shown the potential to be a diagnostic biomarker and a therapeutic agent for prostate cancer. Primates have been the main animal models for studying the biology of this molecule. We have cloned and analyzed the cDNA and promoter region of PSP94 from baboon (Papio anubis). Sequence divergence among baboon, monkey, pig, and human, in both the exons and 5'-flanking region indicates rapid evolution of the PSP94 gene. There are conserved steroid hormone response elements (SHRE) in the promoter region of all three primate species. Multiple, alternative transcripts starting near these SHREs and upstream to the TATA box were identified by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of 5'-cDNA ends (5' RACE) in primate prostatic tissues. This differential transcription initiation may be linked to androgen regulation of PSP94 gene expression. PSP94 transcripts were detected by RT-PCR in a wide variety of mucus-secreting tissues. However, the alternative transcripts were found only in the prostate. The distribution of the PSP94 protein in baboon secretory tissues was also examined by Western blot analysis using a polyclonal antibody against the human homolog. A positive immunoreactive band was detected, but it was weak, due probably to epitope divergence between the two species. In all young, healthy primate animals tested, the level of immunoreactive PSP94 in prostate tissues was lower than expected. In addition, RT-PCR combined with Southern blot analysis on prostate tissues in these animals failed to detect the PSP57 mRNA produced by alternative splicing of PSP94 primary transcript. These observations can be explained by the sexual immaturity and incomplete prostate development in these young primates. This explanation was supported by histological examination of their prostate during PSP94 immunohistochemistry.

Amino Acid Sequence↗
PubMedDate not supplied

Central nervous system serotonin and personality as variables contributing to excessive alcohol consumption in non-human primates.

Non-human primates will readily consume an alcohol solution for its reinforcing effects when such a solution is palatable, with some subjects consuming alcohol to excess. In this review, we discuss variables that contribute to high alcohol consumption and the behaviours that are correlated with it in a non-human primate model. Developmental and behavioural correlates of central nervous system (CNS) serotonergic activity, as measured by concentrations of the serotonin metabolite 5-hydroxyindol-3-ylacetic acid (5-HIAA) in the cerebrospinal fluid (CSF), were used to investigate neurogenetic influences on alcohol consumption, as well as personality traits that characterize excessive alcohol intake. Inter-individual differences in CSF 5-HIAA concentrations were shown to have trait-like qualities, and with stable inter-individual differences across time and settings. Research has shown numerous similarities between human and non-human primates with respect to Type I- and II-like alcohol abuse and their associated behaviours. In the present series of studies, features characteristic of Type I alcohol misuse, such as high levels of anxiety, hypothalamic-pituitary-adrenal output, and situational stress predicted high alcohol intake. Primates with low CSF 5-HIAA concentrations also exhibited behaviours characteristic of Type II alcohol abuse. Principal among the traits that these subjects exhibited were deficits in impulse control. For example, subjects with low CSF 5-HIAA concentrations engaged in spontaneous behaviours that bring reinforcement but placed them at risk, such as entering food baited traps, jumping from dangerous heights to get from one tree to another, and consuming large amounts of alcohol. They can be characterized by other Type II-like deficits, such as impaired social competence, social alienation, and unrestrained, violent aggression. Non-human primates with low CSF 5-HIAA concentrations also exhibited high intrinsic tolerance following modest intakes of alcohol, and high rates of aggression during intoxication. High preferences for sweet solutions were shown to predict excessive alcohol consumption. Maternal and paternal genetic influences played major roles in producing low CNS serotonin function and excessive alcohol consumption. These genetic influences on serotonin function were exacerbated by early rearing experiences, particularly parental deprivation.

Alcoholism↗
PubMed2001

SINE insertions in cladistic analyses and the phylogenetic affiliations of Tarsius bancanus to other primates.

Transpositions of Alu sequences, representing the most abundant primate short interspersed elements (SINE), were evaluated as molecular cladistic markers to analyze the phylogenetic affiliations among the primate infraorders. Altogether 118 human loci, containing intronic Alu elements, were PCR analyzed for the presence of Alu sequences at orthologous sites in each of two strepsirhine, New World and Old World monkey species, Tarsius bancanus, and a nonprimate outgroup. Fourteen size-polymorphic amplification patterns exhibited longer fragments for the anthropoids (New World and Old World monkeys) and T. bancanus whereas shorter fragments were detected for the strepsirhines and the outgroup. From these, subsequent sequence analyses revealed three Alu transpositions, which can be regarded as shared derived molecular characters linking tarsiers and anthropoid primates. Concerning the other loci, scenarios are represented in which different SINE transpositions occurred independently in the same intron on the lineages leading both to the common ancestor of anthropoids and to T. bancanus, albeit at different nucleotide positions. Our results demonstrate the efficiency and possible pitfalls of SINE transpositions used as molecular cladistic markers in tracing back a divergence point in primate evolution over 40 million years old. The three Alu insertions characterized underpin the monophyly of haplorhine primates (Anthropoidea and Tarsioidea) from a novel perspective.

Animals↗
PubMed1999

A macaque model for studying mechanisms controlling oocyte development and maturation in human and non-human primates.

A model to study mechanisms controlling nuclear and cytoplasmic maturation of primate oocytes is being developed in our laboratory. The high incidence of pregnancy failure in women following in-vitro fertilization (IVF) may be partly attributed to inadequate cytoplasmic maturation of oocytes. Advancement of knowledge of mechanisms controlling primate oocyte maturation would have important implications for treatment of human infertility, and would potentially increase numbers of viable non-human primate embryos for biomedical research. Use of a non-human primate model to study oocyte and embryo biology avoids legal, ethical and experimental limitations encountered in a clinical situation. Using this model, the meiotic and developmental capacity of oocytes from three sources have been compared: (i) in-vivo matured oocytes from monkeys stimulated with follicle-stimulating hormone (FSH) and human chorionic gonadotrophin, (ii) in-vitro matured oocytes from monkeys primed with FSH, and (iii) in-vitro matured oocytes from non-stimulated monkeys. This work demonstrates that oocyte developmental competence is likely acquired both during follicle development, before meiotic resumption, and during meiotic progression, concurrent with nuclear maturation. Potential causes of developmental failure of in-vitro matured oocytes, implications for human infertility, and future strategies to study the regulation of primate oocyte maturation are discussed.

Animals↗
PubMed1997

Interleukin-1 beta modulates prostaglandin and progesterone production by primate luteal cells in vitro.

Increasing evidence suggests that cytokine products of the immune system may play a regulatory role in corpus luteum regulation in several species. The role of cytokines in primate luteal function, however, remains unclear. In the present study we examined the effects of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN-gamma) on progesterone and prostaglandin (PGE2, PGF2 alpha) production by primate luteal cells in vitro. Specifically, corpora lutea were removed from normally cycling cynomolgus monkeys (n = 30 corpora lutea) during either the early (Days 3-5 after the estimated LH surge), mid (Days 8-10), or late (Days 12-14) luteal phase of the menstrual cycle. The corpora lutea were dispersed into individual cells using collagenase, DNase, and hyaluronidase. Approximately 50,000 viable luteal cells per tube were incubated in Ham's F-10 medium with increasing concentrations of IL-1 beta (0.1-10 ng/ml), TNF alpha (1-100 ng/ml), or IFN-gamma (10-1000 U/ml) in the presence and absence of hCG for 8 h at 37 degrees C. TNF alpha and IFN-gamma had no effect on progesterone PGE2, or PGF2 alpha production during any phase of the cycle at the doses tested. In contrast, IL-1 beta significantly stimulated PGF2 alpha production in a dose-dependent manner during the mid and late luteal phases (p < 0.05). Human CG alone had no effect on PGE2 or PGF2 alpha production by dispersed luteal cells in vitro but inhibited IL-1 beta-stimulated PGF2 alpha production. As expected, hCG stimulated progesterone production by primate luteal cells in vitro. Interestingly, IL-1 beta inhibited this hCG stimulation of progesterone production. In summary, these date suggest that IL-1 beta is a potentially important modulator of prostaglandin production by the primate corpus luteum. In view of this, cytokine-mediated changes in prostaglandin production by the primate corpus luteum may participate in the physiological regulation of luteal function.

Animals↗
PubMed2001

Oxytocin receptors in non-human primate brain visualized with monoclonal antibody.

The identity of putative oxytocin receptors visualized in autoradiographic studies of primate brain is unclear because the ligand used is much less selective in primate than rodent brains. This study tests the feasibility of utilizing a new monoclonal antibody (MoAb) developed against human uterine OTRs to visualize OTRs in primate brain. A block containing ventral hypothalamus of cynomolgus macaque brain, paraformaldehyde, glutaraldehyde-fixed and paraffin-embedded, and positive control tissue (human endometrium) were sectioned at 8 microm and studied with immunohistochemistry. OTRs were located in fibers in septal nucleus and in both cell bodies and fibers of preoptic area. These results indicate that OTRs in primate brain may be visualized with this MoAb, and are located in primate brain sites linked to the regulation of social behavior.

Animals↗