Womb to womb: Maternal litter size and birth weight but not adult characteristics predict early neonatal death of offspring in the common marmoset monkey.

A singular focus on maternal health at the time of a pregnancy leaves much about perinatal mortality unexplained, especially when there is growing evidence for maternal early life effects. Further, lumping stillbirth and early neonatal death into a single category of perinatal mortality may obscure different causes and thus different avenues of screening and prevention. The common marmoset monkey (Callithrix jacchus), a litter-bearing nonhuman primate, is an ideal species in which to study the independent effects of a mother's early life and adult phenotypes on pregnancy outcomes. We tested two hypotheses in 59 marmoset pregnancies at the Southwest National Primate Research Center and the Barshop Institute for Longevity and Aging Studies. We explored 1) whether pregnancy outcomes were predicted independently by maternal adult weight versus maternal litter size and birth weight, and 2) whether stillbirth and early neonatal death were differentially predicted by maternal variables. No maternal characteristics predicted stillbirth and no maternal adult characteristics predicted early neonatal death. In univariate Poisson models, triplet-born females had a significantly increased rate of early neonatal death (IRR[se] = 3.00[1.29], p = 0.011), while higher birth weight females had a decreased rate (IRR[se] = 0.89[0.05], p = 0.039). In multivariate Poisson models, maternal litter size remained an independent predictor, explaining 13% of the variance in early neonatal death. We found that the later in the first week those neonates died, the more weight they lost. Together these findings suggest that triplet-born and low birth weight females have distinct developmental trajectories underlying greater rates of infant loss, losses that we suggest may be attributable to developmental disruption of infant feeding and carrying. Our findings of early life contributions to adult pregnancy outcomes in the common marmoset disrupt mother-blaming narratives of pregnancy outcomes in humans. These narratives hold that the pregnant person is solely responsible for pregnancy outcomes and the health of their children, independent of socioecological factors, a moralistic framing that has shaped clinical pregnancy management. It is necessary to differentiate temporal trajectories and causes of perinatal loss and view them as embedded in external processes to develop screening, diagnostic, and treatment tools that consider the full arc of a mother's lived experience, from womb to womb and beyond.

Primary neuron and astrocyte cultures from postnatal Callithrix jacchus: a non-human primate in vitro model for research in neuroscience, nervous system aging, and neurological diseases of aging.

The ability to generate in vitro cultures of neuronal cells has been instrumental in advancing our understanding of the nervous system. Rodent models have been the principal source of brain cells used in primary cultures for over a century, providing insights that are widely applicable to human diseases. However, therapeutic agents that showed benefit in rodent models, particularly those pertaining to aging and age-associated dementias, have frequently failed in clinical trials. This discrepancy established a potential "translational gap" between human and rodent studies that may at least partially be explained by the phylogenetic distance between rodent and primate species. Several non-human primate (NHP) species, including the common marmoset (Callithrix jacchus), have been used extensively in neuroscience research, but in contrast to rodent models, practical approaches to the generation of primary cell culture systems amenable to molecular studies that can inform in vivo studies are lacking. Marmosets are a powerful model in biomedical research and particularly in studies of aging and age-associated diseases because they exhibit an aging phenotype similar to humans. Here, we report a practical method to culture primary marmoset neurons and astrocytes from brains of medically euthanized postnatal day 0 (P0) marmoset newborns that yield highly pure primary neuron and astrocyte cultures. Primary marmoset neuron and astrocyte cultures can be generated reliably to provide a powerful NHP in vitro model in neuroscience research that may enable mechanistic studies of nervous system aging and of age-related neurodegenerative disorders. Because neuron and astrocyte cultures can be used in combination with in vivo approaches in marmosets, primary marmoset neuron and astrocyte cultures may help bridge the current translational gap between basic and clinical studies in nervous system aging and age-associated neurological diseases.

Long-term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle-aged marmosets.

Interventions to extend lifespan and improve health with increasing age would have significant impact on a growing aged population. There are now several pharmaceutical interventions that extend lifespan in laboratory rodent models with rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) being the most well studied. In this study, we report on the hematological effects in a cohort of middle-aged common marmosets (Callithrix jacchus) that were enrolled in a study to test the effects of daily rapamycin treatment on aging in this species. In addition, we assessed whether sex was a significant factor in either baseline assessment or as an interaction with rapamycin treatment. Among our cohort at baseline, we found few differences in either basic morphology or hematological markers of blood cell counts, metabolism or inflammation between male and female marmosets. After dosing with rapamycin, surprisingly we found trough blood concentrations of rapamycin were significantly lower in female compared to male marmosets. Despite this pharmacological difference, both sexes had only minor changes in cellular blood counts after 9 months of rapamycin. These data then suggest that the potential clinical hematological side effects of rapamycin are not likely outcomes of long-term rapamycin in relatively healthy, middle-aged marmosets.