A tale of two hierarchies: Hormonal and behavioral factors underlying sex differences in social dominance in cooperative breeding callitrichids.

Callitrichid primates are recognized for high levels of sociality in small groups, their great behavioral flexibility, and single-female dominant hierarchies. Previous work has highlighted that dominant, breeding callitrichids engage in behavioral and hormonal reproductive suppression of related and unrelated subordinates by both producing more offspring, having higher levels of ovulatory hormones, and accessing more sociosexual opportunities. This suppression constitutes a nexus of changes in pituitary responsiveness, ovarian cyclicity, sexual behavior, affiliation, and aggression. In this review, I will highlight important features that characterize callitrichid social hierarchies across broad social contexts. Dominant females sometimes exert reproductive suppression on subordinate nonbreeding females, but this suppression varies across callitrichids based on social stability and changes in group composition, particularly related to the number, experience, and age of nonbreeding subordinates. Meanwhile, dominant males may induce suppression of reproduction in subordinate males, but these effects occur by different behavioral and endocrine mechanisms and to a much lesser extent than their female counterparts; While dominant female callitrichids usually show higher levels of aggression relative to their male counterparts, callitrichids show a general absence of intersexual dominance, likely as an effort of maintaining a cohesive breeding pair within a stable social group and social cooperation. Future efforts are needed to identify precise neuroendocrine mechanisms underlying the presence of sex differences in callitrichid behavior separate from peripheral reproductive function. This is especially important with regard to parental experience, social relationships, development and aging, with larger implications toward understanding sex differences in overall health and wellbeing.

A Comparison of the Ability of Leu8- and Pro8-Oxytocin to Regulate Intracellular Ca2+ and Ca2+-Activated K+ Channels at Human and Marmoset Oxytocin Receptors.

The neurohypophyseal hormone oxytocin (OT) regulates biologic functions in both peripheral tissues and the central nervous system. In the central nervous system, OT influences social processes, including peer relationships, maternal-infant bonding, and affiliative social relationships. In mammals, the nonapeptide OT structure is highly conserved with leucine in the eighth position (Leu8-OT). In marmosets (Callithrix), a nonsynonymous nucleotide substitution in the OXT gene codes for proline in the eighth residue position (Pro8-OT). OT binds to its cognate G protein-coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq). Chinese hamster ovary cells expressing marmoset or human oxytocin receptors (mOTRs or hOTRs, respectively) were used to characterize OT signaling. At the mOTR, Pro8-OT was more efficacious than Leu8-OT in measures of Gq activation, with both peptides displaying subnanomolar potencies. At the hOTR, neither the potency nor efficacy of Pro8-OT and Leu8-OT differed with respect to Gq signaling. In both mOTR- and hOTR-expressing cells, Leu8-OT was more potent and modestly more efficacious than Pro8-OT in inducing hyperpolarization. In mOTR cells, Leu8-OT-induced hyperpolarization was modestly inhibited by pretreatment with pertussis toxin (PTX), consistent with a minor role for Gi/o activation; however, the Pro8-OT response in mOTR and hOTR cells was PTX insensitive. These findings are consistent with membrane hyperpolarization being largely mediated by a Gq signaling mechanism leading to Ca2+-dependent activation of K+ channels. Evaluation of the influence of apamin, charybdotoxin, paxilline, and TRAM-34 demonstrated involvement of both intermediate and large conductance Ca2+-activated K+ channels.

Oxytocin modulates mate-guarding behavior in marmoset monkeys.

In socially-monogamous species, intolerance of interactions between a pairmate and a sexual rival (i.e., mate-guarding) promotes the preservation of long-lasting partnerships. One promising neurobiological candidate for the regulation of mate-guarding behavior in monogamous primates is the oxytocin (OT) system, given its established role in both the development of monogamous bonds and the behavioral processes that facilitate the preservation of those bonds. In this study, male and female marmosets were exposed to a same-sex intruder in their home environment during conditions when their pairmate was present and absent, and across three treatment conditions (OT receptor agonist; saline control; OT receptor antagonist). Saline-treated marmosets spent significantly more time in proximity to the intruder, relative to the empty pairmate enclosure, when their pairmate was absent. However, when marmosets received OT they spent less time in proximity to the intruder, indicating that OT may reduce interest in a same-sex stranger in a territorial context. When their pairmate was present, saline-treated marmosets spent equal time in proximity to both intruder and pairmate; yet when they received OT they spent significantly more time in proximity to the intruder, indicating that OT may increase interest in a same-sex stranger in a mate-guarding context. While OT treatment did not directly influence the expression of aggression, OT system manipulations impacted the expression of selective social interest during an intruder challenge, suggesting that OT may enhance adaptive responses to social challenges. Moreover, these findings add to the converging evidence that the OT system regulates behavioral processes that underlie the preservation of established relationships.

Oxytocin regulates reunion affiliation with a pairmate following social separation in marmosets.

While separation from significant social partners produces a host of neurobiological and behavioral perturbations, including behavioral distress and increased glucocorticoid production, positive social interactions upon reunion are critical for the reestablishment of normative relationship dynamics and the attenuation of the biobehavioral stress response. The hormone oxytocin has critical and pervasive roles in reproductive and behavioral processes across the lifespan, and plays a particularly prominent role in social bonding. In this study, we examined the extent that oxytocin modulates interactions with a pairmate following separation challenges that varied in both social context (isolation; separation) and duration (long; short), in marmosets. We demonstrated that the impact of pharmacological manipulations of the oxytocin system on the expression of affiliation upon reunion depended on both the context and duration of the separation challenge. Specifically, marmosets treated with an oxytocin antagonist spent less time in proximity with their pairmate upon reunion following a long-separation challenge. During the short-separation challenge, marmosets engaged in more social gaze when separated with an opposite-sex stranger, but not when separated with their mate. Furthermore, marmosets that received the most social gaze from opposite-sex strangers spent the most time in proximity with their long-term mate upon reunion. We also showed that marmosets treated with an OT agonist received increased levels of gaze from opposite-sex strangers, but not from their mate. Overall, these results suggest that marmosets are sensitive to the nature of the social interactions during separation, and subsequently alter their expression of affiliation upon reunion with their long-term mate. These findings further implicate oxytocin as a bond-enhancing molecule that regulates the reestablishment of normative levels of affiliation with a mate following separation, and add to the emerging literature that suggests the OT system underlies critical behavioral processes that contribute to the preservation of long-lasting social bonds.

Neuropeptide diversity and the regulation of social behavior in New World primates.

Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology, and have emerged as important modulators of brain function, particularly in the social realm. OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals, but recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date. This review explores these new findings in light of comparative OT/AVP ligand evolution, documents coevolutionary changes in the oxytocin and vasopressin receptors (OTR and V1aR), and highlights the distribution of neuropeptidergic neurons and receptors in the primate brain. Finally, the behavioral consequences of OT and AVP in regulating NWM sociality are summarized, demonstrating important neuromodulatory effects of these compounds and OT ligand-specific influences in certain social domains.

Do marmosets care to share? Oxytocin treatment reduces prosocial behavior toward strangers.

Cooperatively-breeding and socially-monogamous primates, like marmosets and humans, exhibit high levels of social tolerance and prosociality toward others. Oxytocin (OXT) generally facilitates prosocial behavior, but there is growing recognition that OXT modulation of prosocial behavior is shaped by the context of social interactions and by other motivational states such as arousal or anxiety. To determine whether prosociality varies based on social context, we evaluated whether marmoset donors (Callithrix penicillata) preferentially rewarded pairmates versus opposite-sex strangers in a prosocial food-sharing task. To examine potential links among OXT, stress systems, and prosociality, we evaluated whether pretrial cortisol levels in marmosets altered the impact of OXT on prosocial responses. Marmosets exhibited spontaneous prosociality toward others, but they did so preferentially toward strangers compared to their pairmates. When donor marmosets were treated with marmoset-specific Pro(8)-OXT, they exhibited reduced prosociality toward strangers compared to marmosets treated with saline or consensus-mammalian Leu(8)-OXT. When pretrial cortisol levels were lower, marmosets exhibited higher prosociality toward strangers. These findings demonstrate that while marmosets show spontaneous prosocial responses toward others, they do so preferentially toward opposite-sex strangers. Cooperative breeding may be associated with the expression of prosociality, but the existence of a pair-bond between marmoset partners appears to be neither necessary nor sufficient for the expression of spontaneous prosocial responses. Furthermore, high prosociality toward strangers is significantly reduced in marmosets treated with Pro(8)-OXT, suggesting that OXT does not universally enhance prosociality, but, rather OXT modulation of prosocial behavior varies depending on social context.

Behavioral responses to social separation stressor change across development and are dynamically related to HPA activity in marmosets.

Psychosocial stressors activate two distinct stress-response systems, a central, behavioral response, and a peripheral, endocrine response. Both behavioral and endocrine responses to stressors are subject to individual and developmental variables, but it is not known whether stressor induced behaviors are stable across development, and how they correspond with changes in the endocrine component of the stress response. We characterized the development and stability of behavioral responses to a mild psychosocial stressor in marmosets (Callithrix geoffroyi), and assessed the degree to which the behavioral and endocrine stress-response systems were co-activated. The behavioral response to stressors was stable within individuals, but only some stressor-induced behaviors changed as the monkeys developed. Overall, there was more variability in the development of behavioral responses compared to stress-induced endocrine profiles found previously [French et al., 2012. Horm Behav 61:196-203]. In young marmosets, only increased alarm calling was correlated with increased cortisol reactivity, and in older marmosets increased cage manipulations and motor activity were associated with poorer post-stressor cortisol regulation. Because these relationships were so few, we conclude that while the behavioral and endocrine systems follow a similar developmental trajectory, each system maintains a level of independence. Furthermore, the relationship between stressor-induced behaviors and HPA activity changes across development.

Gestational cortisol and social play shape development of marmosets' HPA functioning and behavioral responses to stressors.

Both gestational cortisol exposure (GCE) and variability in postnatal environments can shape the later-life behavioral and endocrine outcomes of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the influence of GCE and social play on HPA functioning in developing marmosets. Maternal urinary cortisol samples were collected across pregnancy to determine GCE for 28 marmoset offspring (19 litters). We administered a social separation stressor to offspring at 6, 12, and 18 months of age, during which we collected urinary cortisol samples and behavioral observations. Increased GCE was associated with increased basal cortisol levels and cortisol reactivity, but the strength of this relationship decreased across age. Increased social play was associated with decreased basal cortisol levels and a marginally greater reduction in cortisol reactivity as offspring aged, regardless of offspring GCE. Thus, GCE is associated with HPA functioning, but socially enriching postnatal environments can alter the effects associated with increased fetal exposure to glucocorticoids.

Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.

Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat C. difficile infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. Prior work indicates that FMT is safe in marmosets and may successfully mediate gut microbiome function and host health. This narrative review (1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, (2) summarizes the prior use of FMT in marmosets, (3) outlines a protocol synthesized from prior literature for studying FMT in aging marmosets, and (4) describes limitations, knowledge gaps, and future research needs in this field.

Stress reactivity in young marmosets (Callithrix geoffroyi): ontogeny, stability, and lack of concordance among co-twins.

Variation in response styles in the hypothalamic-pituitary-adrenal (HPA) axis are known to be predictors of short- and long-term health outcomes. The nature of HPA responses to stressors changes with developmental stage, and some components of the stress response exhibit long-term individual consistency (i.e., are trait-like) while others are transient or variable (i.e., state-like). Here we evaluated the response of marmoset monkeys (Callithrix geoffroyi) to a standardized social stressor (social separation and exposure to a novel environment) at three different stages of development: juvenile, subadult, and young adult. We monitored levels of urinary cortisol (CORT), and derived multiple measures of HPA activity: Baseline CORT, CORT reactivity, CORT Area Under the Curve (AUC), and CORT regulation. Juvenile marmosets exhibited the most dramatic stress response, had higher AUCs, and tended to show poorer regulation. While baseline CORT and CORT regulation were not consistent within an individual across age, CORT reactivity and measures of AUC were highly correlated across time; i.e., individuals with high stress reactivity and AUC as juveniles also had high measures as subadults and adults, and vice-versa. Marmoset co-twins did not exhibit similar patterns of stress reactivity. These data suggest that regardless of the source of variation in stress response styles in marmosets, individually-distinctive patterns are established by six months of age, and persist for at least a year throughout different phases of marmoset life history.

Natural variation in gestational cortisol is associated with patterns of growth in marmoset monkeys (Callithrix geoffroyi).

High levels of prenatal cortisol have been previously reported to retard fetal growth. Although cortisol plays a pivotal role in prenatal maturation, heightened exposure to cortisol can result in lower body weights at birth, which have been shown to be associated with adult diseases like hypertension and cardiovascular disease. This study examines the relationship between natural variation in gestational cortisol and fetal and postnatal growth in marmoset monkeys. Urinary samples obtained during the mother's gestation were analyzed for cortisol. Marmoset body mass index (BMI) was measured from birth through 540 days in 30- or 60-day intervals. Multi-level modeling was used to test if marmoset growth over time was predicted by changes in gestational cortisol controlling for time, sex, litter, and litter size. The results show that offspring exposed to intra-uterine environments with elevated levels of cortisol had lower linear BMI rates of change shortly after birth than did offspring exposed to lower levels of cortisol, but exhibited a higher curvilinear growth rate during adolescence. Average daily change in gestational cortisol during the first trimester had a stronger relationship with postnatal growth than change during the third trimester. Higher exposure to cortisol during gestation does alter developmental trajectories, however there appears to be a catch-up period during later post-natal growth. These observations contribute to a larger discussion about the relationship of maternal glucocorticoids on offspring development and the possibility of an earlier vulnerable developmental window.

Describing ovarian cycles, pregnancy characteristics, and the use of contraception in female white-faced marmosets, Callithrix geoffroyi.

Endocrine data and characteristics of nonconceptive ovarian cycling and pregnancy are limited within the genus Callithrix to the common marmoset (C. jacchus) and Wied's black tufted-ear marmoset (C. kuhlii). This article presents patterns of urinary pregnanediol-3-glucuronide (PdG) excretion, as determined by enzyme immunoassay, throughout the course of ovarian cycling and pregnancy in white-faced marmosets (C. geoffroyi). Furthermore, characteristics of reproductive parameters including litter size, duration of gestation, maternal age, and information about ovarian cycling following administration of contraceptives are also described. A steep increase in PdG, an indication of ovulation, characterizes normative ovarian cycles, with peak-to-peak intervals between cycles being 27.82 ± 1.49 days in length. PdG excretion (µg/mg Cr) across pregnancy peaked during the 1st and 2nd trimesters (1st = 20.71 ± 2.98, 2nd = 21.16 ± 2.60) and declined gradually to near preconception levels over the 3rd trimester until parturition (3rd = 5.74 ± 1.60). Gestation lasted 148.55 ± 1.89 days. Most pregnancies (82.8%) resulted in an immediate postpartum ovulation (PPO) of 17.45 ± 2.22 days with 58.3% of PPOs resulting in conception. No differences in PdG excretion during the 1st trimester between full pregnancies and miscarriages were found, and pregnancy characteristics such as litter size, duration of gestation, and maternal age were not associated with PdG concentrations. Administration of cloprostenol resulted in shorter peak-to-peak cycle durations, but ovulation was detectable with similar concentrations of peak PdG to a normal nonconceptive cycle. Conversely, medroxyprogesterone acetate (DMPA) injections resulted in little to no PdG excretion across the ovarian cycle. Both methods of contraception providing effective prevention of conception. Overall, these results show that strong similarities in reproductive parameters persist within the genus Callithrix and to a lesser extent across the Callitrichidae family.

Captive Common Marmosets (Callithrix jacchus) Are Colonized throughout Their Lives by a Community of Bifidobacterium Species with Species-Specific Genomic Content That Can Support Adaptation to Distinct Metabolic Niches.

The common marmoset (Callithrix jacchus) is an omnivorous New World primate whose diet in the wild includes large amounts of fruit, seeds, flowers, and a variety of lizards and invertebrates. Marmosets also feed heavily on tree gums and exudates, and they have evolved unique morphological and anatomical characteristics to facilitate gum feeding (gummivory). In this study, we characterized the fecal microbiomes of adult and infant animals from a captive population of common marmosets at the Callitrichid Research Center at the University of Nebraska at Omaha under their normal dietary and environmental conditions. The microbiomes of adult animals were dominated by species of Bifidobacterium, Bacteroides, Prevotella, Phascolarctobacterium, Megamonas, and Megasphaera. Culturing and genomic analysis of the Bifidobacterium populations from adult animals identified four known marmoset-associated species (B. reuteri, B. aesculapii, B. myosotis, and B. hapali) and three unclassified taxa of Bifidobacterium that are phylogenetically distinct. Species-specific quantitative PCR (qPCR) confirmed that these same species of Bifidobacterium are abundant members of the microbiome throughout the lives of the animals. Genomic loci in each Bifidobacterium species encode enzymes to support growth and major marmoset milk oligosaccharides during breastfeeding; however, metabolic islands that can support growth on complex polysaccharide substrates in the diets of captive adults (pectin, xyloglucan, and xylan), including loci in B. aesculapii that can support its unique ability to grow on arabinogalactan-rich tree gums, were species-specific. IMPORTANCEBifidobacterium species are recognized as important, beneficial microbes in the human gut microbiome, and their ability colonize individuals at different stages of life is influenced by host, dietary, environmental, and ecological factors, which is poorly understood. The common marmoset is an emerging nonhuman primate model with a short maturation period, making this model amenable to study the microbiome throughout a life history. Features of the microbiome in captive marmosets are also shared with human gut microbiomes, including abundant populations of Bifidobacterium species. Our studies show that several species of Bifidobacterium are dominant members of the captive marmoset microbiome throughout their life history. Metabolic capacities in genomes of the marmoset Bifidobacterium species suggest species-specific adaptations to different components of the captive marmoset diet, including the unique capacity in B. aesculapii for degradation of gum arabic, suggesting that regular dietary exposure in captivity may be important for preserving gum-degrading species in the microbiome.

Sex Bias in Gut Microbiome Transmission in Newly Paired Marmosets (Callithrix jacchus).

Social behavior can alter the microbiome composition via transmission among social partners, but there have been few controlled experimental studies of gut microbiome transmission among social partners in primates. We collected longitudinal fecal samples from eight unrelated male-female pairs of marmoset monkeys prior to pairing and for 8 weeks following pairing. We then sequenced 16S rRNA to characterize the changes in the gut microbiome that resulted from the pairing. Marmoset pairs had a higher similarity in gut microbiome communities after pairing than before pairing. We discovered sex differences in the degrees of change in gut microbiome communities following pairing. Specifically, the gut microbiome communities in males exhibited greater dissimilarity from the prepairing stage (baseline) than the gut microbiome communities in females. Conversely, females showed a gradual stabilization in the rate of the gut microbiome community turnover. Importantly, we found that the male fecal samples harbored more female-source gut microbes after pairing, especially early in pairing (paired test, P < 0.05), possibly linked to sex bias in the frequencies of social behavior. From this controlled study, we report for the first time that pair-living primates undergo significant changes in gut microbiome during pairing and that females transmit more microbes to their partners than males do. The potential biases influencing which microbes are transmitted on the basis of sex and whether they are due to sex biases in other behavioral or physiological features need to be widely investigated in other nonhuman primates and humans in the future.IMPORTANCE In this controlled study, we collected longitudinal fecal samples from 16 male and female marmoset monkeys for 2 weeks prior to and for 8 weeks after pairing in male-female dyads. We report for the first time that marmoset monkeys undergo significant changes to the gut microbiome following pairing and that these changes are sex-biased; i.e., females transmit more microbes to their social partners than males do. Marmosets exhibit pair bonding behavior such as spatial proximity, physical contact, and grooming, and sex biases in these behavioral patterns may contribute to the observed sex bias in social transmission of gut microbiomes.

Fecal Short-Chain Fatty Acid Concentrations Increase in Newly Paired Male Marmosets (Callithrix jacchus).

The role by which the gut microbiome influences host health (e.g., energy equilibrium and immune system) may be partly mediated by short-chain fatty acids, which are bacterial fermentation products from the dietary fibers. However, little is known about longitudinal changes in gut microbiome metabolites during cohabitation alongside social contact. In common marmosets (Callithrix jacchus), the gut microbiome community is influenced by social contact, as newly paired males and females develop convergent microbial profiles. Here, we monitored the dynamics of short-chain fatty acid concentrations in common marmoset feces from the prepairing (PRE) to postpairing (POST) stages. In males, we observed that the concentrations of acetate, propionate, isobutyrate, and isovalerate significantly increased in the POST stage compared to the PRE stage. However, no significant changes were found in females. We further found that the propionate concentration was significantly positively correlated with the abundance of Phascolarctobacterium in the male feces. Thus, the sex difference in the changes in the concentrations of short-chain fatty acids might be related to sex-biased gut microbiome transmission after pairing. We suggest that the significant changes in the gut microbiomes and some short-chain fatty acids of the common marmoset during cohabitation may contribute to physiological homeostasis during pairing.IMPORTANCE This study addressed a knowledge gap about longitudinal changes in the gut microbiome metabolites during animal pairing. This research in the laboratory common marmoset can control for the confounding factors such as diet and other environmental conditions. Phascolarctobacterium showed the highest contribution to the sex-biased transmission of the female to the male after pairing. Here, we observed the sex difference in the increase in short-chain fatty acid concentration in the feces of newly paired marmosets, which may be caused by the sex-biased gut microbiome transmission after pairing.

Leu8 and Pro8 oxytocin agonism differs across human, macaque, and marmoset vasopressin 1a receptors.

Oxytocin (OXT) is an important neuromodulator of social behaviors via activation of both oxytocin receptors (OXTR) and vasopressin (AVP) 1a receptors (AVPR1a). Marmosets are neotropical primates with a modified OXT ligand (Pro8-OXT), and this ligand shows significant coevolution with traits including social monogamy and litter size. Pro8-OXT produces more potent and efficacious responses at primate OXTR and stronger behavioral effects than the consensus mammalian OXT ligand (Leu8-OXT). Here, we tested whether OXT/AVP ligands show differential levels of crosstalk at primate AVPR1a. We measured binding affinities and Ca2+ signaling responses of AVP, Pro8-OXT and Leu8-OXT at human, macaque, and marmoset AVPR1a. We found that AVP binds with higher affinity than OXT across AVPR1a, and marmoset AVPR1a show a 10-fold lower OXT binding affinity compared to human and macaque AVPR1a. Both Leu8-OXT and Pro8-OXT produce a less efficacious response than AVP at human AVPR1a and higher efficacious response than AVP at marmoset AVPR1a. These data suggest that OXT might partially antagonize endogenous human AVPR1a signaling and enhance marmoset AVPR1a signaling. These findings aid in further understanding inconsistencies observed following systemic intranasal administration of OXT and provide important insights into taxon-specific differences in nonapeptide ligand/receptor coevolution and behavior.

Oxytocin structure and function in New World monkeys: from pharmacology to behavior.

Oxytocin (OT) is a hypothalamic nonapeptide that mediates a host of physiological and behavioral processes including reproductive physiology and social attachments. While the OT sequence structure is highly conserved among mammals, New World monkeys (NWMs) represent an unusual "hot spot" in OT structure variability among mammals. At least 6 distinct OT ligand variants among NWMs exist, yet it is currently unclear whether these evolved structural changes result in meaningful functional consequences. NWMs offer a new area to explore how these modifications to OT and its canonical G-protein coupled OT receptor (OTR) may mediate specific cellular, physiological and behavioral outcomes. In this review, we highlight relationships between OT ligand and OTR structural variability, specifically examining coevolution between OT ligands, OTRs, and physiological and behavioral phenotypes across NWMs. We consider whether these evolved modifications to the OT structure alter pharmacological profiles at human and marmoset OTRs, including changes to receptor binding, intracellular signaling and receptor internalization. Finally, we evaluate whether exogenous manipulation using OT variants in marmoset monkeys differentially enhance or impair behavioral processes involved in social relationships between pairmates, opposite-sex strangers, and parents and their offspring. Overall, it appears that changes to OT ligands in NWMs result in important changes ranging from cellular signaling to broad measures of social behavior.

Social Monogamy in Nonhuman Primates: Phylogeny, Phenotype, and Physiology.

Monogamy as a social system has been both a scientific puzzle and a sociocultural issue for decades. In this review, we examine social monogamy from a comparative perspective with a focus on primates, our closest genetic relatives. We break down monogamy into component elements, including pair-bonding and partner preference, mate guarding or jealousy, social attachment, and biparental care. Our survey of primates shows that not all features are present in species classified as socially monogamous, in the same way that human monogamous relationships may not include all elements-a perspective we refer to as "monogamy à la carte." Our review includes a survey of the neurobiological correlates of social monogamy in primates, exploring unique or common pathways for the elemental components of monogamy. This compilation reveals that the components of monogamy are modulated by a suite of androgenic steroids, glucocorticoid hormones, the nonapeptide hormones oxytocin and vasopressin, and other neurotransmitter systems (e.g., dopamine and opioids). We propose that efforts to understand the biological underpinnings of complex human and animal sociosexual relationships will be well served by exploring individual phenotypic traits, as opposed to pursuing these questions with the assumption that monogamy is a unitary trait or a species-specific characteristic.

Inequity aversion strategies between marmosets are influenced by partner familiarity and sex but not oxytocin.

Cooperation among individuals depends, in large part, on a sense of fairness. Many cooperating non-human primates (NHPs) show inequity aversion, (i.e., negative responses to unequal outcomes), and these responses toward inequity likely evolved as a means to preserve the advantages of cooperative relationships. However, marmosets (Callithrix spp.) tend to show little or no inequity aversion, despite the high occurrence of prosociality and cooperative-breeding in callitrichid monkeys. Oxytocin [OXT] has been implicated in a wide variety of social processes, but little is known about whether OXT modulates inequity aversion toward others. We used a tray pulling task to evaluate whether marmosets would donate superior rewards to their long-term pairmate or an opposite-sex stranger following OXT, OXT antagonist, and saline treatments. We found that marmosets show inequity aversion, and this inequity aversion is socially- and sex-specific. Male marmosets show inequity aversion toward their pairmates but not strangers, and female marmosets do not show inequity aversion. OXT treatments did not significantly influence inequity aversion in marmosets. While OXT may modulate prosocial preferences, the motivations underlying cooperative relationships, such as inequity aversion, are multifaceted. More research is needed to evaluate the evolutionary origins, biological processes, and social contexts that influence complex phenotypes like inequity aversion. Inequity aversion can differ within species in important and distinct ways including between individuals who do and do not share a cooperative relationship. Overall, these findings support the view that inequity aversion is an important behavioural strategy for the maintenance of cooperative relationships.

Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates.

BACKGROUND: Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates. METHODS: We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). RESULTS: IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence. CONCLUSIONS: In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin.