Julienne N Rutherford

Interests

Teaching

Anatomy and Physiology of Reproduction, Pregnancy, and LactationWomen's HealthGrantwriting

Research

Fetal and placental development and function, women’s health, evolutionary medicine and biomedicine, human and non-human primate reproduction and pregnancy, pregnancy loss, developmental origins of adult health and social disparities, postpartum hemorrhage, fetal brain development and evolution, midwifery, reproductive justice, safe and inclusive academic workplaces

Courses

Scholarly Contributions

Journals/Publications

• Hemphill, N., Crooks, N., Zhang, W., Erbe, K., Rutherford, J. N., Liese, K. L., Pearson, P., Stewart, K., Reed, L., Tussing-Humphreys, L., & Koenig, M. D. (2023). Obstetric Experiences of Young Black Mothers: An Intersectional Perspective. Social Science and Medicine, 317(114604).
• Koenig, M. D., Crooks, N., Burton, T., Li, Y., Hemphill, N., Erbe, K., Rutherford, J. N., Liese, K. L., Pearson, P., Stewart, K., Kessee, N., Reed, L., & Tussing-Humphreys, L. (2023). Structural violence and stress experiences of young Black mothers. Journal of Racial and Ethnic Health Disparities. doi:https://doi.org/10.1007/s40615-023-01661-y
• Rutherford, J. N. (2023). Revealing the political project of pregnancy: Review of Weighing the Future: Race, Science, and Pregnancy Trials in the Postgenomic Era, by Natali Valdez. (2022). University of California Press. Oakland, CA.. American Journal of Biological Anthropology. doi:https://doi.org/10.1002/ajpa.24870
• Rutherford, J. N., Kapoor, A., Snowdon, C. T., Ross, C. N., Tardif, S. D., & Ziegler, T. E. (2023).

  Timing of the luteal-placental shift is delayed with additional fetuses in litter-bearing callitrichid monkeys, Saguinus oedipus and Callithrix jacchus

  . General and Comparative Endocrinology. doi:10.1016/j.ygcen.2022.114195
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  The luteal-placental shift is an important milestone of mammalian pregnancy signifying when endocrine control of pregnancy shifts from the corpus luteum of the ovary to the placenta. The corpus luteum is maintained by chorionic gonadotropin (CG). Upon sufficient placental maturation, CG production wanes, the corpus luteum involutes, and control is shifted to the placenta, one consequence of which is a midgestational rise in glucocorticoid production, especially cortisol and cortisone, by both mother and fetus. Glucocorticoids are involved in initiating parturition, prenatal programming of offspring phenotype, and maturing fetal organs. Limited evidence from human pregnancy suggests that the timing of this shift is delayed in twin pregnancies, but little is known about the timing of the luteal-placental shift in litter-bearing monkeys from the primate family Callitrichidae. Here we provide evidence from cotton-top tamarins (Saguinus oedipus) and common marmosets (Callithrix jacchus) of longer duration of elevated CG associated with multiple infant births compared to single births. Urinary profiles from cotton-top tamarins demonstrate that the decline of the extended elevation of CG precedes the onset of the midpregnancy sustained rise in glucocorticoids; this shift occurs later with an increase from one to two fetuses carried to term. In the common marmoset, the onset of the sustained rise of glucocorticoids in maternal urine is also delayed with an increase in infant number. Total urinary glucocorticoid levels during the last half of gestation increase monthly but do not differ by infant number. The significant delay in the luteal-placental shift suggests a longer period of placental maturation is needed to support a greater number of fetuses.
• Rutherford, J. N., Uwizeye, G., & Thayer, Z. M. (2023).

  Associations between duration of first trimester intrauterine exposure to genocide against the Tutsi and health outcomes in adulthood

  . American Journal of Biological Anthropology. doi:10.1002/ajpa.24708
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  Hundreds of thousands of Rwandans were conceived during the 1994 genocide against the Tutsi, including thousands conceived by genocidal rape. We explore whether the duration of first trimester exposure to the genocide is associated with variation in adult mental health outcomes in individuals exposed to varying degrees of genocide-related stress in utero.We recruited 30 Rwandans conceived via genocidal rape, 31 Rwandans conceived by genocide survivors not raped, and 30 individuals of Rwandan-descent who were conceived outside of Rwanda at the time of the genocide (control group). Individuals were age- and sex-matched across groups. Adult mental health was assessed through standardized questionnaires for vitality, anxiety, and depression.Among the genocide only group, a longer duration of first trimester prenatal exposure was associated with higher anxiety scores and lower vitality (both p < 0.010), and higher depression scores (p = 0.051). Duration of first trimester exposure was not associated with any measures of mental health among the genocidal rape or control group.Duration of exposure to genocide in the first trimester of gestation was associated with variation in adult mental health among the genocide only group. The lack of association between duration of first trimester exposure to genocide and adult mental health in the genocidal rape group may reflect the fact that stress associated with conception through rape persisted beyond the genocide period itself, encompassing all of gestation and likely beyond. Geopolitical and community interventions are needed in the context of extreme events during pregnancy to mitigate adverse intergenerational outcomes.
• Bostwick, W. B., Rutherford, J. N., Patil, C. L., Ploutz-Snyder, R. J., Spetz, J., Stephenson, R., & Yakusheva, O. (2021). Envisioning a more expansive future for multidisciplinary nursing scholarship and education. Nursing Outlook, 69(4), 507-509.
• Kim, I. J., Lanthier, P. A., Clark, M. J., De La Barrera, R. A., Tighe, M. P., Szaba, F. M., Travis, K. L., Low-Beer, T. C., Cookenham, T. S., Lanzer, K. G., Bernacki, D. T., Johnson, L. L., Schneck, A. A., Ross, C. N., Tardif, S. D., Layne-Colon, D., Mdaki, S. D., Dick, E. J., Chuba, C., , Gonzalez, O., et al. (2022). Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets. NPJ vaccines, 7(1), 9.
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  Zika virus (ZIKV) is a mosquito-borne arbovirus that can cause severe congenital birth defects. The utmost goal of ZIKV vaccines is to prevent both maternal-fetal infection and congenital Zika syndrome. A Zika purified inactivated virus (ZPIV) was previously shown to be protective in non-pregnant mice and rhesus macaques. In this study, we further examined the efficacy of ZPIV against ZIKV infection during pregnancy in immunocompetent C57BL6 mice and common marmoset monkeys (Callithrix jacchus). We showed that, in C57BL/6 mice, ZPIV significantly reduced ZIKV-induced fetal malformations. Protection of fetuses was positively correlated with virus-neutralizing antibody levels. In marmosets, the vaccine prevented vertical transmission of ZIKV and elicited neutralizing antibodies that remained above a previously determined threshold of protection for up to 18 months. These proof-of-concept studies demonstrate ZPIV's protective efficacy is both potent and durable and has the potential to prevent the harmful consequence of ZIKV infection during pregnancy.
• Uwizeye, G., DeVon, H. A., McCreary, L. L., Patil, C. L., Thayer, Z. M., & Rutherford, J. N. (2022). Children born of genocidal rape: What do we know about their experiences and needs?. Public Health Nursing, 39(1), 350-359.
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  An often under addressed and tragic legacy of genocide is the conception of children from rape. While the experience has been documented from their mothers' perspective, the perspectives and needs of individuals born of genocidal rape has been under-studied.
• VanSickle, C., Liese, K. L., & Rutherford, J. N. (2022). Textbook typologies: Challenging the myth of the perfect obstetric pelvis. Anatomical Record, 305(4), 952-967.
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  Medical education's treatment of obstetric-related anatomy exemplifies historical sex bias in medical curricula. Foundational obstetric and midwifery textbooks teach that clinical pelvimetry and the Caldwell-Moloy classification system are used to assess the pelvic capacity of a pregnant patient. We describe the history of these techniques-ostensibly developed to manage arrested labors-and offer the following criticisms. The sample on which these techniques were developed betrays the bias of the authors and does not represent the sample needed to address their interest in obstetric outcomes. Caldwell and Moloy wrote as though the size and shape of the bony pelvis are the primary causes of "difficult birth"; today we know differently, yet books still present their work as relevant. The human obstetric pelvis varies in complex ways that are healthy and normal such that neither individual clinical pelvimetric dimensions nor the artificial typologies developed from these measurements can be clearly correlated with obstetric outcomes. We critique the continued inclusion of clinical pelvimetry and the Caldwell-Moloy classification system in biomedical curricula for the racism that was inherent in the development of these techniques and that has clinical consequences today. We call for textbooks, curricula, and clinical practices to abandon these outdated, racist techniques. In their place, we call for a truly evidence-based practice of obstetrics and midwifery, one based on an understanding of the complexity and variability of the physiology of pregnancy and birth. Instead of using false typologies that lack evidence, this change would empower both pregnant people and practitioners.
• Rutherford, J. N., Ross, C. N., Ziegler, T., Burke, L. A., Steffen, A. D., Sills, A., Layne Colon, D., deMartelly, V. A., Narapareddy, L. R., & Tardif, S. D. (2021). Womb to womb: Maternal litter size and birth weight but not adult characteristics predict early neonatal death of offspring in the common marmoset monkey. PloS One, 16(6), e0252093.
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  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.
• Uwizeye, G., Thayer, Z. M., DeVon, H. A., McCreary, L. L., McDade, T. W., Mukamana, D., Park, C., Patil, C. L., & Rutherford, J. N. (2021). Double Jeopardy: Young adult mental and physical health outcomes following conception via genocidal rape during the 1994 genocide against the Tutsi in Rwanda. Social Science & Medicine, 278, 113938.
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  Rwandans conceived by rape during the 1994 genocide against the Tutsi have endured a violent beginning and a troubled childhood. Given compelling evidence of the influence of prenatal environments and adverse childhood experiences (ACEs) on future health, these individuals are at high risk of poor mental and physical health outcomes. The purpose of the study was to characterize mental and physical health outcomes in young adults who were exposed prenatally to maternal stress due to the genocide in general and those conceived by genocidal rape, and to determine whether ACEs compound these effects. Ninety-one 24-year-old Rwandans - 30 conceived by genocidal rape, 31 born of genocide survivors not raped, and a control group of 30 born of women with neither exposure - completed the Adverse Childhood Experiences International Questionnaire and measures of multiple physical and mental health characteristics. Data were collected from March 7 to April 6, 2019. Findings demonstrated that 1) individuals conceived during the genocide had poorer mental function (p = 0.002) and higher scores in post-traumatic stress disorder (PTSD), anxiety, depression, physical function, pain intensity, and sleep disturbance compared to young adults who were not exposed to genocide (all p 
• Kuzawa, C. W., Adair, L., Bechayda, S. A., Borja, J. R., Carba, D. B., Duazo, P. L., Eisenberg, D. T., Georgiev, A. V., Gettler, L. T., Lee, N. R., Quinn, E. A., Rosenbaum, S., Rutherford, J. N., Ryan, C. P., & McDade, T. W. (2020). Evolutionary life history theory as an organising framework for cohort studies: insights from the Cebu Longitudinal Health and Nutrition Survey. Annals of Human Biology, 47(2), 94-105.
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  By tracking a group of individuals through time, cohort studies provide fundamental insights into the developmental time course and causes of health and disease. Evolutionary life history theory seeks to explain patterns of growth, development, reproduction and senescence, and inspires a range of hypotheses that are testable using the longitudinal data from cohort studies. Here we review two decades of life history theory-motivated work conducted in collaboration with the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a birth cohort study that enrolled more than 3000 pregnant women in the Philippines in 1983 and has since followed these women, their offspring and grandoffspring. This work has provided evidence that reproduction carries "costs" to cellular maintenance functions, potentially speeding senescence, and revealed an unusual form of genetic plasticity in which the length of telomeres inherited across generations is influenced by reproductive timing in paternal ancestors. Men in Cebu experience hormonal and behavioural changes in conjunction with changes in relationship and fatherhood status that are consistent with predictions based upon other species that practice bi-parental care. The theoretical expectation that early life cues of mortality or environmental unpredictability will motivate a "fast" life history strategy are confirmed for behavioural components of reproductive decision making, but not for maturational tempo, while our work points to a broader capacity for early life developmental calibration of systems like immunity, reproductive biology and metabolism. Our CLHNS findings illustrate the power of life history theory as an integrative, lifecourse framework to guide longitudinal studies of human populations.
• Narapareddy, L., Wildman, D. E., Armstrong, D. L., Weckle, A., Bell, A. F., Patil, C. L., Tardif, S. D., Ross, C. N., & Rutherford, J. N. (2020). Maternal weight affects placental DNA methylation of genes involved in metabolic pathways in the common marmoset monkey (Callithrix jacchus). American Journal of Primatology, 82(3), e23101.
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  Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including the regulation of glycolytic and lipid metabolic processes pathways.
• Thayer, Z. M., Rutherford, J., & Kuzawa, C. W. (2020). The Maternal Nutritional Buffering Model: an evolutionary framework for pregnancy nutritional intervention. Evolution, Medicine, and Public Health, 2020(1), 14-27.
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  Evidence that fetal nutrition influences adult health has heightened interest in nutritional interventions targeting pregnancy. However, as is true for other placental mammals, human females have evolved mechanisms that help buffer the fetus against short-term fluctuations in maternal diet and energy status. In this review, we first discuss the evolution of increasingly elaborate vertebrate strategies of buffering offspring from environmental fluctuations during development, including the important innovation of the eutherian placenta. We then present the Maternal Nutritional Buffering Model, which argues that, in contrast to many micronutrients that must be derived from dietary sources, the effects of short-term changes in maternal macronutrient intake during pregnancy, whether due to a deficit or supplementation, will be minimized by internal buffering mechanisms that work to ensure a stable supply of essential resources. In contrast to the minimal effects of brief macronutrient supplementation, there is growing evidence that sustained improvements in early life and adult pre-pregnancy nutrition could improve birth outcomes in offspring. Building on these and other observations, we propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself. Our model leads to the prediction that birth weight will be more strongly influenced by the mother's chronic pre-pregnancy nutrition than by pregnancy diet, and highlights the need for policy solutions aimed at optimizing future, intergenerational health outcomes. Lay summary: We propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself.
• Powell-Roach, K. L., Yao, Y., Rutherford, J. N., Schlaeger, J. M., Patil, C. L., Suarez, M. L., Shuey, D., Angulo, V., Carrasco, J., Ezenwa, M. O., Fillingim, R. B., Wang, Z. J., Molokie, R. E., & Wilkie, D. J. (2019). Thermal and mechanical quantitative sensory testing values among healthy African American adults. Journal of Pain Research, 12, 2511-2527.
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  Only a few studies have reported quantitative sensory testing (QST) reference values for healthy African Americans, and those studies are limited in sample size and age of participants. The study purpose was to characterize QST values in healthy, pain-free African American adults and older adults whose prior pain experiences and psychological status were also measured. We examined the QST values for differences by sex, age, and body test site.
• Rutherford, J. N., deMartelly, V. A., Ragsdale, H. B., Avila, J. L., Lee, N. R., & Kuzawa, C. W. (2019). Global population variation in placental size and structure: Evidence from Cebu, Philippines. Placenta, 85, 40-48.
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  Placental morphology influences the intrauterine environment and fetal growth, which help set life-course health trajectories across generations. Little is known about placental characteristics in populations with chronic nutritional insufficiency where birth weights tend to be lower, and how these relationships between birth and placental weights vary across populations.
• Riesche, L., Tardif, S. D., Ross, C. N., deMartelly, V. A., Ziegler, T., & Rutherford, J. N. (2018). The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity. American Journal of Physiology: Regulatory, integrative and comparative physiology, 314(5), R684-R692.
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  Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.
• Roach, K. L., Hershberger, P. E., Rutherford, J. N., Molokie, R. E., Wang, Z. J., & Wilkie, D. J. (2018). The AVPR1A Gene and Its Single Nucleotide Polymorphism rs10877969: A Literature Review of Associations with Health Conditions and Pain. Pain Management Nursing : official journal of the American Society of Pain Management Nurses, 19(4), 430-444.
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  Pain is the quintessential symptom for individuals suffering from sickle cell disease (SCD). Although the degree of suffering and the cost of treatment are staggering, SCD continues to be grossly understudied, including a lack of data for pain-related genes and prevalence of polymorphisms in this population. This lack of data adds to the inadequacy of pain therapy in this population. Pain genetics investigators have recently examined allele frequencies of single-nucleotide polymorphisms from candidate genes in people who have SCD. One of the genes identified was the arginine vasopressin receptor 1A gene (AVPR1A) and its associated single-nucleotide polymorphism (SNP) rs10877969. Progress in explaining pain-related polymorphisms associated with SCD can be facilitated by understanding the literature. Aim/Design: The purpose of this literature review was to describe mechanisms of the polymorphic gene AVPR1A and the phenotypic variations associated with its SNPs relative to health conditions and pain.
• Ruchob, R., Rutherford, J. N., & Bell, A. F. (2018). A Systematic Review of Placental Biomarkers Predicting Small-for-Gestational-Age Neonates. Biological Research for Nursing, 20(3), 272-283.
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  Neonates born small for gestational age (SGA) face increased risk of neonatal mortality, childhood developmental problems, and adult disease. The placenta is a key factor in SGA development because of its multiple biological processes that underlie fetal growth. However, valid and reliable placental biomarkers of SGA have not been determined.
• Seferovic, M., Sánchez-San Martín, C., Tardif, S. D., Rutherford, J., Castro, E. C., Li, T., Hodara, V. L., Parodi, L. M., Giavedoni, L., Layne-Colon, D., Tamhankar, M., Yagi, S., Martyn, C., Reyes, K., Suter, M. A., Aagaard, K. M., Chiu, C. Y., & Patterson, J. L. (2018). Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities. Scientific reports, 8(1), 6851.
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  During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.
• Clancy, K. B., Nelson, R. G., Rutherford, J. N., & Hinde, K. (2014). Survey of academic field experiences (SAFE): trainees report harassment and assault. PloS One, 9(7), e102172.
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  Little is known about the climate of the scientific fieldwork setting as it relates to gendered experiences, sexual harassment, and sexual assault. We conducted an internet-based survey of field scientists (N = 666) to characterize these experiences. Codes of conduct and sexual harassment policies were not regularly encountered by respondents, while harassment and assault were commonly experienced by respondents during trainee career stages. Women trainees were the primary targets; their perpetrators were predominantly senior to them professionally within the research team. Male trainees were more often targeted by their peers at the research site. Few respondents were aware of mechanisms to report incidents; most who did report were unsatisfied with the outcome. These findings suggest that policies emphasizing safety, inclusivity, and collegiality have the potential to improve field experiences of a diversity of researchers, especially during early career stages. These include better awareness of mechanisms for direct and oblique reporting of harassment and assault and, the implementation of productive response mechanisms when such behaviors are reported. Principal investigators are particularly well positioned to influence workplace culture at their field sites.
• Harris, R. A., Tardif, S. D., Vinar, T., Wildman, D. E., Rutherford, J. N., Rogers, J., Worley, K. C., & Aagaard, K. M. (2014). Evolutionary genetics and implications of small size and twinning in callitrichine primates. Proceedings of the National Academy of Sciences of the United States of America, 111(4), 1467-72.
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  New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi's monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations.
• Rutherford, J. N., deMartelly, V. A., Layne Colon, D. G., Ross, C. N., & Tardif, S. D. (2014). Developmental origins of pregnancy loss in the adult female common marmoset monkey (Callithrix jacchus). PloS One, 9(5), e96845.
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  The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction.
• Tardif, S. D., Power, M. L., Ross, C. N., & Rutherford, J. N. (2013). Body mass growth in common marmosets: toward a model of pediatric obesity. American Journal of Physical Anthropology, 150(1), 21-8.
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  While much is known about adult obesity in nonhuman primates, very little is known regarding development of childhood adiposity. As small monkeys that are easy to handle and have a relatively fast life history, common marmoset monkeys (Callithrix jacchus) offer interesting opportunities to examine the question of fat versus lean mass growth in a nonhuman primate. This article provides an overview of our understanding of early life growth in mass in marmoset monkeys, based primarily upon our past 20 years of research, culminating in our recent findings on early life obesity in this species. Common marmosets display variance in early life growth patterns that is related to both pre- and postnatal factors and the marmoset uterine environment is exquisitely designed to reflect resources available for the gestation of multiple offspring, making them an interesting model of developmental programming. We have demonstrated that obesity can be generated in very early life in captive marmosets, with excess adiposity evident by one month of age, making this species a potentially valuable model in which to study pediatric obesity and its sequelae. Birth weight is associated with adiposity in animals vulnerable to obesity. Early life exposure to higher fat diets enhances the chances of postweaning obesity development. However, overall higher food consumption is also associated with obesity development at later ages. One unexpected finding in our studies has been the relatively high body fat percentage of neonatal (12-18%) marmosets suggesting that hypotheses regarding the uniqueness of high human neonatal adiposity merit further examination.
• DeMartelly, V., Hurley, P., Lawrence, M., Redmond, D. E., & Rutherford, J. (2012). Comparison of fresh to fixed weights of the vervet monkey (Chlorocebus sabaeus) placenta and its relation to gestational age. Journal of Medical Primatology, 41(3), 158-62.
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  Focus on the placenta as an agent of fetal development and offspring health outcomes is growing. Primate research facilities or zoos may collect and fix placental tissue for long-term storage, but little is known about the effects of formalin fixation on the non-human primate placenta.
• Rutherford, J. N. (2012). Toward a nonhuman primate model of fetal programming: phenotypic plasticity of the common marmoset fetoplacental complex. Placenta, 33 Suppl 2, e35-9.
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  Nonhuman primates offer unique opportunities as animal models in the study of developmental programming and the role of the placenta in developmental processes. All primates share fundamental similarities in life history and reproductive biology. Thus, insights gleaned from studies of nonhuman primates have a higher degree of biological salience to human biology than do studies of rodents or agricultural animals. The common marmoset monkey is a small-bodied primate from South America that produces litters of dizygotic fetuses that share a single placental mass. This natural variation allows us to model different intrauterine conditions and associated fetoplacental phenotypes. The marmoset placenta is phenotypically plastic according to litter size. Triplet litters are characterized by low individual fetal weights and significantly more efficient placentas and attendant alterations to the microscopic architecture and endocrine function, thus modeling a nutrient restricted intrauterine environment. Consistent with this model, triplet neonates experience a higher risk of perinatal mortality and an increased likelihood of elevated adult weight. Recent evidence has shown that the intrauterine experience of females has an impact on their own pregnancy outcomes in adulthood: triplet females experience significantly greater pregnancy loss than do twin females. The marmoset monkey thus represents a potential powerful nonhuman primate model of multiple pregnancies, restrictive prenatal experiences, and differential reproductive outcomes in adulthood, which may have important implications for studying the impact of in vitro fertilization on adult reproductive health. It is still too early to determine exactly what developmental pathways lead to this disparity or what specific role the placenta plays; future work on this front will be critical to establish the marmoset as an important model of fetal programming of reproductive function in adulthood and across generations.
• Abrams, E. T., & Rutherford, J. N. (2011). Framing postpartum hemorrhage as a consequence of human placental biology: an evolutionary and comparative perspective. American Anthropologist, 113(3), 417-30.
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  Postpartum hemorrhage (PPH), the leading cause of maternal mortality worldwide, is responsible for 35 percent of maternal deaths. Proximately, PPH results from the failure of the placenta to separate from the uterine wall properly, most often because of impairment of uterine muscle contraction. Despite its prevalence and its well-described clinical manifestations, the ultimate causes of PPH are not known and have not been investigated through an evolutionary lens. We argue that vulnerability to PPH stems from the intensely invasive nature of human placentation. The human placenta causes uterine vessels to undergo transformation to provide the developing fetus with a high plane of maternal resources; the degree of this transformation in humans is extensive. We argue that the particularly invasive nature of the human placenta increases the possibility of increased blood loss at parturition. We review evidence suggesting PPH and other placental disorders represent an evolutionarily novel condition in hominins.
• Rutherford, J. N., McDade, T. W., Feranil, A. B., Adair, L. S., & Kuzawa, C. W. (2010). High prevalence of low HDL-c in the Philippines compared to the US: population differences in associations with diet and BMI. Asia Pacific Journal of Clinical Nutrition, 19(1), 57-67.
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  Cardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol (HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to US women participating in the National Health and Nutrition Examination Survey (NHANES, n=477). We conducted multiple regression models to assess the relationship between lipid components, body mass index, and dietary variables in the two populations. We measured the prevalence of lipid phenotypes, and logistic regression models determined the predictors of the isolated low HDL-c phenotype. High density lipoprotein cholesterol was lower in the Philippines (40.8+/-0.2 mg/dL) than in NHANES (60.7+/-0.7 mg/dL). The prevalence of the isolated low HDL-c phenotype was 28.8%, compared to 2.10% in NHANES. High prevalence among Filipinos was relatively invariant across all levels of BMI, but was strongly inversely related to BMI in NHANES and exhibited only at the BMI>25 kg/m2 threshold. Diet did not consistently predict the low-HDL phenotype in Filipinos. Filipino women exhibit a high prevalence of the isolated low HDL-c phenotype, which is largely decoupled from anthropometric factors. The relationship of CVD to population variation in dyslipidemia and body composition needs further study, particularly in populations where the burden of cardiovascular and metabolic disease is rapidly increasing.

Presentations

• Rutherford, J. N. (2023, February). Keynote Address: Follow the Red Brick Road: Unexpected adventures in anthropology. Faber Scholar Address, World Anthropology Day. Miami University: Miami University Department of Anthropology.
• Uwizeye, G., & Rutherford, J. N. (2023, October). Whose research is it? Knowledge creation with and for survivors of the 1994 genocide against the Tutsi. Decolonizing Biological Anthropology Workshop. Charlotte, NC: American Journal of Biological Anthropology.