Annual Review of Animal Biosciences

Reproductive and Metabolic Health Following Exposure to Environmental Chemicals: Mechanistic Insights from Mammalian Models
Bellingham M, Evans NP, Lea RG, Padmanabhan V and Sinclair KD
The decline in human reproductive and metabolic health over the past 50 years is associated with exposure to complex mixtures of anthropogenic environmental chemicals (ECs). Real-life EC exposure has varied over time and differs across geographical locations. Health-related issues include declining sperm quality, advanced puberty onset, premature ovarian insufficiency, cancer, obesity, and metabolic syndrome. Prospective animal studies with individual and limited EC mixtures support these observations and provide a means to investigate underlying physiological and molecular mechanisms. The greatest impacts of EC exposure are through programming of the developing embryo and/or fetus, with additional placental effects reported in eutherian mammals. Single-chemical effects and mechanistic studies, including transgenerational epigenetic inheritance, have been undertaken in rodents. Important translational models of human exposure are provided by companion animals, due to a shared environment, and sheep exposed to anthropogenic chemical mixtures present in pastures treated with sewage sludge (biosolids). Future animal research should prioritize EC mixtures that extend beyond a single developmental stage and/or generation. This would provide a more representative platform to investigate genetic and underlying mechanisms that explain sexually dimorphic and individual effects that could facilitate mitigation strategies.
Progress Toward Genetic Rescue of the Northern White Rhinoceros ()
Korody ML and Hildebrandt TB
The northern white rhinoceros (NWR) is functionally extinct, with only two nonreproductive females remaining. However, because of the foresight of scientists, cryopreserved cells and reproductive tissues may aid in the recovery of this species. An ambitious program of natural and artificial gamete and in vitro embryo generation was first outlined in 2015, and many of the proposed steps have been achieved. Multiple induced pluripotent stem cell lines have been established, primordial germ cell-like cells have been generated, oocytes have been collected from the remaining females, blastocysts have been cryopreserved, and the closely related southern white rhinoceros (SWR) is being established as a surrogate. Recently, the first successful embryo transfer in SWR demonstrated that embryos can be generated by in vitro fertilization and cryopreserved. We explore progress to date in using advanced cellular technologies to save the NWR and highlight the necessary next steps to ensure a viable population for reintroduction. We roll out a holistic rescue approach for a charismatic megavertebrate that includes the most advanced cellular technologies, which can provide a blueprint for other critically endangered mammals. We also provide a detailed discussion of the remaining questions in such an upgraded conservation program.
Ruminating on Bovine Implantation: Its Importance in Fertility, Food Production, Conservation, and Health
Amelkina O, Gardner S, Edge JC, Butt Z, Tinning H and Forde N
Implantation in cattle is a key developmental checkpoint for pregnancy success. It involves careful spatiotemporal changes to the transcriptional landscape of the endometrium, with the heterogeneous nature of the endometrium increasing the complexity of understanding of the mechanism involved. Implantation is impacted by the developmental competency of the embryo, use of assisted reproductive technologies, and the environment in which this process occurs. We identify the factors that most impact the implantation process in cattle and highlight how it differs with that in other placental mammals. We propose the major areas that lack evidence are the mechanism(s) by which implantation itself occurs and how different stressors alter this process. Our understanding is hindered by a lack of appropriate in vitro models; however, development of novel 3D tools and available data sets will further elucidate the implantation process. Perhaps more importantly, this will develop methods to mitigate against these stressors to improve implantation success and offspring health.
Evolution of 3D Chromatin Folding
Álvarez-González L and Ruiz-Herrera A
Studies examining the evolution of genomes have focused mainly on sequence conservation. However, the inner working of a cell implies tightly regulated crosstalk between complex gene networks controlled by small dispersed regulatory elements of physically contacting DNA regions. How these different levels of chromatin organization crosstalk in different species underpins the potential for genome evolutionary plasticity. We review the evolution of chromatin organization across the Animal Tree of Life. We introduce general aspects of the mode and tempo of genome evolution to later explore the multiple layers of genome organization. We argue that both genome and chromosome size modulate patterns of chromatin folding and that chromatin interactions facilitate the formation of lineage-specific chromosomal reorganizations, especially in germ cells. Overall, analyzing the mechanistic forces involved in the maintenance of chromatin structure and function of the germ line is critical for understanding genome evolution, maintenance, and inheritance.
Rumen-Targeted Mining of Enzymes for Bioenergy Production
Cann I, Cheng Y, Alhawsawi MAB, Moran M, Li Y, Gong T, Zhu W and Mackie RI
Second-generation biofuel production, which aims to convert lignocellulose to liquid transportation fuels, could be transformative in worldwide energy portfolios. A bottleneck impeding its large-scale deployment is conversion of the target polysaccharides in lignocellulose to their unit sugars for microbial fermentation to the desired fuels. Cellulose and hemicellulose, the two major polysaccharides in lignocellulose, are complex in nature, and their interactions with pectin and lignin further increase their recalcitrance to depolymerization. This review focuses on the intricate linkages present in the feedstocks of interest and examines the potential of the enzymes evolved by microbes, in the microbe/ruminant symbiotic relationship, to depolymerize the target polysaccharides. We further provide insights to how a rational and more efficient assembly of rumen microbial enzymes can be reconstituted for lignocellulose degradation. We conclude by expounding on how gains in this area can impact the sustainability of both animal agriculture and the energy sector.
Lipotoxicity and Oocyte Quality in Mammals: Pathogenesis, Consequences, and Reversibility
Meulders B, Marei WFA, Loier L and Leroy JLMR
Metabolic stress conditions are often characterized by upregulated lipolysis and subsequently increased serum free fatty acid (FFA) concentrations, leading to the uptake of FFAs by non-adipose tissues and impairment of their function. This phenomenon is known as lipotoxicity. The increased serum FFA concentrations are reflected in the ovarian follicular fluid, which can have harmful effects on oocyte development. Several studies using in vitro and in vivo mammalian models showed that altered oocyte metabolism, increased oxidative stress, and mitochondrial dysfunction are crucial mechanisms underlying this detrimental impact. Ultimately, this can impair offspring health through the persistence of defective mitochondria in the embryo, hampering epigenetic reprogramming and early development. In vitro and in vivo treatments to enhance oocyte mitochondrial function are increasingly being developed. This can help to improve pregnancy rates and safeguard offspring health in metabolically compromised individuals.
The Path to Net-Zero in Dairy Production: Are Pronounced Decreases in Enteric Methane Achievable?
Beauchemin KA, Kebreab E, Cain M and VandeHaar MJ
Achieving net-zero greenhouse gas (GHG) emissions in dairy production will require >50% reduction in enteric methane (CH) emissions together with elimination of emissions from feed production, additional carbon sequestration, reduction in manure emissions, anaerobic digestion of manure, and decreased reliance on fossil fuel energy. Over past decades, improved production efficiency has reduced GHG intensity of milk production (i.e., emissions per unit of milk) in the United States, but this trend will continue only if cows are bred for increased efficiency. Genetic selection of low-CH-producing animals, diet reformulation, use of feed additives, and vaccination show tremendous potential for enteric CH mitigation; however, few mitigation strategies are currently available, and added cost without increased revenue is a major barrier to implementation. Complete elimination of CH emissions from dairying is likely not possible without negatively affecting milk production; thus, offsets and removals of other GHGs will be needed to achieve net-zero milk production.
A One Health Approach to Reducing Livestock Disease Prevalence in Developing Countries: Advances, Challenges, and Prospects
Lane JK, Kelly T, Bird B, Chenais E, Roug A, Vidal G, Gallardo R, Zhou H, VanHoy G and Smith W
Challenges in livestock production in developing countries are often linked to a high disease prevalence and may be related to poor husbandry, feeding, and nutrition practices, as well as to inadequate access to preventive veterinary care. Structural barriers including chronic poverty, gender roles, inadequate supply chains, and limitations in surveillance infrastructure further complicate progress. Despite many challenges, the livestock sector substantially contributes to agricultural GDP, and reducing livestock disease prevalence is a goal for many countries. One Health initiatives that work across disciplines and sectors to reduce livestock diseases are underway around the world and use integrated approaches that consider the connections between humans, animals, and their shared environments. The growing recognition of the role livestock play in sustainability and livelihoods, as well as their involvement in zoonotic disease transmission and global health security, has highlighted the need for disease reduction strategies as described in this review.
A Passion for Small Things and Staying Primed: My Career in Virology and Immunology
Saif LJ
A love of science and animals, perseverance, and happenstance propelled my career in veterinary virology and immunology. I have focused on deadly enteric and respiratory viral infections in neonatal livestock and humans with an aim to understand their prevalence, pathogenesis, interspecies transmission, and immunity and develop vaccines. Research on animal coronaviruses (CoVs), including their broad interspecies transmission, provided a foundation to understand emerging zoonotic fatal human respiratory CoVs [severe acute respiratory syndrome, Middle East respiratory syndrome, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)] and reverse zoonosis of SARS-CoV-2 to animals. A highlight of my early research was the discovery of the gut-mammary gland-sIgA axis, documenting a common mucosal immune system. The latter remains pivotal to designing maternal vaccines for passive immunity in neonates. Our discovery and innovative cell propagation of fastidious human and animal rotaviruses and caliciviruses and their infectivity in germ-free animals has provided cell-adapted and animal disease models for ongoing virologic and immunologic investigations and vaccines. Nevertheless, besides the research discoveries, my lasting legacy remains the outstanding mentees who have enriched my science and my life.
Convergent Evolution of Pregnancy in Vertebrates
Whittington CM, Hodgson MJ and Friesen CR
Viviparity (live birth) represents a significant evolutionary innovation that has emerged in hundreds of lineages of invertebrate and vertebrate animals. The evolution of this trait from the ancestral state of egg laying has involved complex morphological, behavioral, physiological, and genetic changes, which enable internal development of embryos within the female reproductive tract. Comparable changes have also occurred in oviparous, brooding species that carry developing embryos in locations other than the female reproductive tract. This review explores the taxonomic distribution of vertebrate viviparity and brooding (collectively termed pregnancy), discusses the adaptations associated with internal incubation, and examines hypotheses surrounding the evolution of pregnancy in different lineages. Understanding the mechanisms that have led to the emergence of this trait can illuminate questions about the evolution of reproductive complexity and the processes that led to the emergence of evolutionary innovations that have shaped the remarkable diversity of Earth's fauna.
The Geometric Framework for Nutrition and Its Application to Rodent Models
Senior AM, Raubenheimer D, Couteur DGL and Simpson SJ
Rodents have been the primary model for mammalian nutritional physiology for decades. Despite an extensive body of literature, controversies remain around the effects of specific nutrients and total energy intake on several aspects of nutritional biology, even in this well-studied model. One approach that is helping to bring clarity to the field is the geometric framework for nutrition (GFN). The GFN is a multidimensional paradigm that can be used to conceptualize nutrition and nutritional effects, design experiments, and interpret results. To date, more than 30 publications have applied the GFN to data from rodent models of nutrition. Here we review the major conclusions from these studies. We pay particular attention to the effects of macronutrients on satiety, glucose metabolism, lifespan and the biology of aging, reproductive function, immune function, and the microbiome. We finish by highlighting several knowledge gaps that became evident upon reviewing this literature.
Molecular Innovations Shaping Beak Morphology in Birds
Cheng Y, Miller MJ and Lei F
The beak, a pivotal evolutionary trait characterized by high morphological diversity and plasticity, has enabled birds to survive mass extinction events and subsequently radiate into diverse ecological niches worldwide. This remarkable ecological adaptability underscores the importance of uncovering the molecular mechanisms shaping avian beak morphology, particularly benefiting from the rapidly advancing archives of genomics and epigenomics. We review the latest advancements in understanding how genetic and epigenetic innovations control or regulate beak development and drive beak morphological adaptation and diversification over the past two decades. We conclude with several recommendations for future endeavors, expanding to more bird lineages, with a focus on beak shape and the lower beak, and conducting functional experiments. By directing research efforts toward these aspects and integrating advanced omics techniques, the complex molecular mechanisms involved in avian beak evolution and morphogenesis will be deeply interpreted.
The Rhesus Macaque as an Animal Model for Human Nutrition: An Ecological-Evolutionary Perspective
Cui Z, Dong Y, Sholl J, Lu J and Raubenheimer D
Nutrition is a complex and contested area in biomedicine, which requires diverse evidence sources. Nonhuman primate models are considered an important biomedical research tool because of their biological similarities to humans, but they are typically used with little explicit consideration of their ecology and evolution. Using the rhesus macaque (RM), we consider the potential of nutritional ecology for enriching the use of primates as models for human nutrition. We introduce some relevant aspects of RM evolutionary and social ecology and discuss two examples where they have been used in biomedical research: obesity and aging. We next consider how insights from nutritional ecology can help inform and direct the use of RM as a biomedical model. We conclude by illustrating how conceptual tools might inform the use of RM as a model for human nutrition and extracting insights from RM that might be relevant to broader theoretical considerations around animal model systems.
Parasites in a Changing World: Troublesome or in Trouble?
Wood CL
There are plenty of reasons to believe that parasite populations will respond to biodiversity loss, warming, pollution, and other forms of global change. But will global change enhance transmission, increasing the incidence of troublesome parasites that put people, livestock, and wildlife at risk? Or will parasite populations decline in abundance-or even become extinct-suggesting trouble on the horizon for parasite biodiversity? Here, I explain why answers have thus far eluded us and suggest new lines of research that would advance the field. Data collected to date suggest that parasites can respond to global change with increases or decreases in abundance, depending on the driver and the parasite. The future will certainly bring outbreaks of some parasites, and these should be addressed to protect human and ecosystem health. But troublesome parasites should not consume all of our research effort, because this changing world contains many parasite species that are in trouble.
Chromosome Engineering: Technologies, Applications, and Challenges
Mao Y, Zhao Y, Zhou Q and Li W
Chromosome engineering is a transformative field at the cutting edge of biological science, offering unprecedented precision in manipulating large-scale genomic DNA within cells. This discipline is central to deciphering how the multifaceted roles of chromosomes-guarding genetic information, encoding sequence positional information, and influencing organismal traits-shape the genetic blueprint of life. This review comprehensively examines the technological advancements in chromosome engineering, which center on engineering chromosomal rearrangements, generating artificial chromosomes, de novo synthesizing chromosomes, and transferring chromosomes. Additionally, we introduce the application progress of chromosome engineering in basic and applied research fields, showcasing its capacity to deepen our knowledge of genetics and catalyze breakthroughs in therapeutic strategies. Finally, we conclude with a discussion of the challenges the field faces and highlight the profound implications that chromosome engineering holds for the future of modern biology and medical applications.
Comparative Genomics and Epigenomics of Transcriptional Regulation
Zhou H, Clark E, Guan D, Lagarrigue S, Fang L, Cheng H, Tuggle CK, Kapoor M, Wang Y, Giuffra E and Egidy G
Transcriptional regulation in response to diverse physiological cues involves complicated biological processes. Recent initiatives that leverage whole genome sequencing and annotation of regulatory elements significantly contribute to our understanding of transcriptional gene regulation. Advances in the data sets available for comparative genomics and epigenomics can identify evolutionarily constrained regulatory variants and shed light on noncoding elements that influence transcription in different tissues and developmental stages across species. Most epigenomic data, however, are generated from healthy subjects at specific developmental stages. To bridge the genotype-phenotype gap, future research should focus on generating multidimensional epigenomic data under diverse physiological conditions. Farm animal species offer advantages in terms of feasibility, cost, and experimental design for such integrative analyses in comparison to humans. Deep learning modeling and cutting-edge technologies in sequencing and functional screening and validation also provide great promise for better understanding transcriptional regulation in this dynamic field.
No More Extinctions: Recovering Australia's Biodiversity
Woinarski JCZ, Garnett ST and Legge SM
Most conservation programs and laws aim to prevent extinction. However, there is a gulf between such aspirations and the current reality of escalating biodiversity loss. This review focuses on efforts to prevent extinctions in Australia, but much of this consideration is likely to apply globally. As context, we consider the reasons for trying to prevent extinction, review Australia's extinction record, and note that there are likely to be many more extinctions than formally recognized. We describe recent cases where conservation actions have prevented extinction. We note that extinction is a pathway rather than solely an endpoint, and many decisions made or not made on that pathway can determine the fate of species. We conclude that all looming extinctions can and should be prevented. This will require transformational change in legislation, increased resourcing, more consideration of poorly known species, and increased societal recognition of the need to be responsible for the care of country.
Translational Relevance and Future Integration of the Oncopig Cancer Model in Preclinical Applications
Elkhadragy L, Gaba RC, Niemeyer MM, Schook LB and Schachtschneider KM
Porcine cancer models offer a valuable platform for evaluating interventions such as devices, surgeries, and locoregional therapies, which are often challenging to test in mouse models. In addition to size and anatomical similarities with humans, pigs share greater similarities in genetics, immunity, drug metabolism, and metabolic rate with humans as compared to mouse models, increasing their translational relevance. This review focuses on the Oncopig Cancer Model, a genetically engineered porcine model designed to recapitulate human cancer. Harboring a transgenic cassette that expresses oncogenic mutant and under control of a Cre-Lox system, the Oncopig allows temporal and spatial control of tumor induction. Its versatility has enabled the development of diverse cancer models including liver, pancreatic, lung, and bladder cancer. Serving as a clinically relevant model for human cancer, the Oncopig addresses unmet clinical needs and holds immense promise for advancing preclinical cancer research and therapeutic development.
An Evolutionary Perspective on Dog Behavioral Genetics
Lord KA, Chen FL and Karlsson EK
Dogs have played an outsized role in the field of behavioral genetics since its earliest days. Their unique evolutionary history and ubiquity in the modern world make them a potentially powerful model system for discovering how genetic changes lead to changes in behavior. Genomic technology has supercharged this potential by enabling scientists to sequence the DNA of thousands of dogs and test for correlations with behavioral traits. However, fractures in the early history of animal behavior between biological and psychological subfields may be impeding progress. In addition, canine behavioral genetics has included almost exclusively dogs from modern breeds, who represent just a small fraction of all dog diversity. By expanding the scope of dog behavior studies, and incorporating an evolutionary perspective on canine behavioral genetics, we can move beyond associations to understanding the complex interactions between genes and environment that lead to dog behavior.
Integrated Genomic Approaches to Characterize and Mitigate Heat Stress in Poultry
Schmidt CJ and Lamont SJ
With the burgeoning human population, climate change, and expansion of poultry production in hot climates, it is imperative to aid global food security by enhancing the resilience of thermally challenged poultry. As a complement to management approaches used to mitigate heat stress, we give selected examples of recent studies on heat stress in poultry using various omics technologies. An integrated analysis of positional and functional candidate genes is provided, highlighting the most prominent pathways involved in the heat stress response. We finish by discussing efficient strategies to enhance thermal tolerance of poultry by genomics approaches, advocating for preservation of biodiversity that may provide beneficial allelic variation, and identifying current and future challenges in producing climate-resilient poultry.
Improving Nutrition Security in Low- and Middle-Income Countries and the Role of Animal-Source Foods
Paro FR, Davour R, Acosta D, Mechlowitz K, Tiwari C and McKune SL
Nutrition security is challenging in regions where resources are limited and food production is naturally constrained. In low- and middle-income countries (LMICs), undernutrition is high for many reasons, including lack of nutritional diversity and low high-quality protein content. Interest in the role of animal-source food (ASF) in reducing nutrition insecurity is increasing, as evidence from LMICs suggests that consumption of ASF is strongly associated with reduction in stunting, improved diet quality, and overall nutrition, particularly in early stages of life. We review the strengths and limitations of ASF consumption in terms of accessibility, safety, and nutritional benefits compared to non-ASF sources. We present a critical discussion on existing barriers to ASF consumption and its future directions in LMICs. Understanding the role of ASF in improving nutrition security in LMICs is crucial to optimizing public health, designing appropriate interventions, and implementing effective policy in resource-poor settings.