Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.

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.

Evolution in reproductive tempo and investment across the Peromyscus radiation.

Mammals display diverse reproductive strategies, however, the ultimate and proximate mechanisms that underlie this diversity and its composite traits remain poorly understood from both evolutionary and physiological perspectives. The Peromyscus genus of rodents, which is found throughout the north and central Americas, has diversified along life history gradients, varying both within and among species in reproductive strategies. This variation provides a useful model for studying reproductive diversity. Here, we combine a literature review with new analyses of captive colony breeding records from six Peromyscus species to assess our current understanding of how plasticity and local adaptation contribute to diversity in two classes of reproductive traits: phenology and litter investment. There is substantial evidence that many traits underlying phenology and litter investment have diverged among populations in ways that are likely to be locally adaptive, though plasticity in these traits remains common. However, these conclusions are largely based on data collected from the two most widespread Peromyscus species: P. maniculatus and P. leucopus. The majority of Peromyscus species diversity remains understudied regarding reproductive phenology and litter traits. We conclude by discussing key challenges and considerations relevant to using Peromyscus as a mammalian model for reproductive trait diversity and evolution moving forward.