Search for: All records

Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia. 

Residence at high altitude is consistently associated with low birthweight among placental mammals. This reduction in birthweight influences long-term health trajectories for both the offspring and mother. However, the physiological processes that contribute to fetal growth restriction at altitude are still poorly understood, and thus our ability to safely intervene remains limited. One approach to identify the factors that mitigate altitude-dependent fetal growth restriction is to study populations that are protected from fetal growth restriction through evolutionary adaptations (e.g., high altitude-adapted populations). Here, we examine human gestational physiology at high altitude from a novel evolutionary perspective that focuses on patterns of physiological plasticity, allowing us to identify 1) the contribution of specific physiological systems to fetal growth restriction and 2) the mechanisms that confer protection in highland-adapted populations. Using this perspective, our review highlights two general findings: first, that the beneficial value of plasticity in maternal physiology is often dependent on factors more proximate to the fetus; and second, that our ability to understand the contributions of these proximate factors is currently limited by thin data from altitude-adapted populations. Expanding the comparative scope of studies on gestational physiology at high altitude and integrating studies of both maternal and fetal physiology are needed to clarify the mechanisms by which physiological responses to altitude contribute to fetal growth outcomes. The relevance of these questions to clinical, agricultural, and basic research combined with the breadth of the unknown highlight gestational physiology at high altitude as an exciting niche for continued work. 

ABSTRACT High-altitude environments, characterized by low oxygen levels and low ambient temperatures, have been repeatedly colonized by small altricial mammals. These species inhabit mountainous regions year-round, enduring chronic cold and hypoxia. The adaptations that allow small mammals to thrive at altitude have been well studied in non-reproducing adults; however, our knowledge of adaptations specific to earlier life stages and reproductive females is extremely limited. In lowland natives, chronic hypoxia during gestation affects maternal physiology and placental function, ultimately limiting fetal growth. During post-natal development, hypoxia and cold further limit growth both directly by acting on neonatal physiology and indirectly via impacts on maternal milk production and care. Although lowland natives can survive brief sojourns to even extreme high altitude as adults, reproductive success in these environments is very low, and lowland young rarely survive to sexual maturity in chronic cold and hypoxia. Here, we review the limits to maternal and offspring physiology – both pre-natal and post-natal – that highland-adapted species have overcome, with a focus on recent studies on high-altitude populations of the North American deer mouse (Peromyscus maniculatus). We conclude that a combination of maternal and developmental adaptations were likely to have been critical steps in the evolutionary history of high-altitude native mammals. 

Scientific conferences incorporate diversity-focused events into their programming to increase their diversity and inclusivity and to improve the conference experience for scientists from underrepresented groups (URGs). While simply adding diversity-focused events to conferences is positive, maximizing their impact requires that conferences organize and schedule these events to minimize well-acknowledged, problematic patterns such as the minority tax. To our knowledge, the programming of diversity-focused events at conferences has not been systematically reviewed to identify the extent of these shortcomings and how they can be addressed.