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

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

Genetic Diversity in Oxytocin Ligands and Receptors in New World Monkeys

Oxytocin (OXT) is an important neurohypophyseal hormone that influences wide spectrum of reproductive and social processes. Eutherian mammals possess a highly conserved sequence of OXT (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly). However, in this study, we sequenced the coding region for OXT in 22 species covering all New World monkeys (NWM) genera and clades, and characterize five OXT variants, including consensus mammalian Leu8-OXT, major variant Pro8-OXT, and three previously unreported variants: Ala8-OXT, Thr8-OXT, and Phe2-OXT. Pro8-OXT shows clear structural and physicochemical differences from Leu8-OXT. We report multiple predicted amino acid substitutions in the G protein- coupled OXT receptor (OXTR), especially in the critical N-terminus, which is crucial for OXT recognition and binding. Genera with same Pro8-OXT tend to cluster together on a phylogenetic tree based on OXTR sequence, and we demonstrate significant coevolution between OXT and OXTR. NWM species are characterized by high incidence of social monogamy, and we document an association between OXTR phylogeny and social monogamy. Our results demonstrate remarkable genetic diversity in the NWM OXT/OXTR system, which can provide a foundation for molecular, pharmacological, and behavioral studies of the role of OXT signaling in regulating complex social phenotypes

Will You Still Like Me Tomorrow?: Long term Changes in Sociosexual Relationships in Marmosets (Callithrix jacchus)

This abstract has been removed to protect the intellectual property of the project

Sex Bias in Gut Microbiome Transmission in Newly Paired Marmosets (\u3ci\u3eCallithrix jacchus\u3c/i\u3e)

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 com-munities 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 re-port 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

Analysis of <i>N</i>-terminus of OXTR in primates.

<p><b>A.</b> Alignment of the 38 OXTR amino acids in New World monkeys (NWM, rectangle framed) and non-NWM primates. Sequences for non-NWM primates accessed from NCBI, UCSC or Ensembl. A dot represents identity with human OXTR amino acid. <b>B.</b> The isoelectric point (pI) and grand average of hydropathicity (GRAVY) of OXT (top) and <i>N</i>-termini of OXTR (bottom). Plots include Pro⁸-OXT species (<i>Callithrix</i>) and non-Pro⁸-OXT species (<i>Homo</i>, <i>Macaca</i>, <i>Alouatta</i>, <i>Pithecia</i> and <i>Cacajao</i>). All OXT ligands show the same pI value, but exhibit marked differences in GRAVY, with Pro⁸-OXT being most hydrophilic. <i>N</i>-termini of <i>Callithrix</i> OXTR, possessing lower pI and GRAVY values, are distinct from <i>N</i>-termini from other representative species. Symbol colors for OXTR correspond to ligand variation. Larger negative numbers in GRAVY indicate a more hydrophilic molecule; pI values less than 7.3 indicate that molecules carry a net negative charge, relative to the pH in brain tissue.</p

Five OXT ligands identified in New World monkeys and their distribution in a phylogenetic tree generated from OXTR nucleotide sequences.

<p><b>A.</b> 2-D structure of mammalian consensus Leu⁸-OXT, and other four OXT variants, including Pro⁸-OXT, Ala⁸-OXT, Thr⁸-OXT and Phe²-OXT. The 2-D structures of oxytocin ligands were created in ChemDraw Pro 12.0. Different colors indicate different OXT ligands. <b>B.</b> OXT ligands (representing by different colors as in Fig 1A) are distributed in a phylogenetic tree inferred from OXTR nucleotides. If posterior probability (upper) and bootstrap support (lower) are < 50, no value is shown at nodes. Scale bar indicates the branch length in nucleotide substitutions per site.</p

Sex Bias in Gut Microbiome Transmission in Newly Paired Marmosets (\u3ci\u3eCallithrix jacchus\u3c/i\u3e)

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 com-munities 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 re-port 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