Developmental Plasticity Research Articles

Effects and phenotypic consequences of transient thyrotoxicosis and hypothyroidism at different stages of zebrafish Danio rerio (Teleostei; Cyprinidae) skeleton development.

The effects and consequences of changes in thyroid hormones (THs) level are among the actively studied topics in teleost developmental and evolutionary biology. In most of the experimental models used, the altered hormonal status (either hypo- or hyperthyroidism) is a stable characteristic of the developing organism, and the observed phenotypic outcomes are the cumulative consequences of multiple TH-induced developmental changes. Meanwhile, the influence of the transient fluctuations of TH content on skeleton development has been much less studied. Here, we present experimental data on the developmental effects and phenotypic consequences of transient, pharmacologically induced thyrotoxicosis and hypothyroidism at different stages of ossified skeleton patterning in zebrafish. According to the results, the skeleton structures differed in TH sensitivity. Some showed a notable shift in the developmental timing and rate, while other demonstrated little or no response to changes in TH content. The developmental stages also differed in TH sensitivity. We identified a relatively short developmental period, during which changes in TH level significantly increased the developmental instability and plasticity, leading to phenotypic consequences comparable to those in fish with a persistent hypo- or hyperthyroidism. These findings allow this period to be considered as a critical developmental window.

Developmental mechanisms linking deprivation and threat to psychopathology and school outcomes.

Decades of evidence have elucidated associations between early adversity and risk for negative outcomes. However, traditional conceptualizations of the biologic embedding of adversity ignore neuroscientific principles which emphasize developmental plasticity. Dimensional models suggest that separate dimensions of experiences shape behavioral development differentially. We hypothesized that deprivation would be associated with higher psychopathology and lower academic achievement through executive function and effortful control, while threat would do so through observed, and parent reported emotional reactivity. In this longitudinal study of 206 mother-child dyads, we test these theories across the first 7 years of life. Threat was measured by the presence of domestic violence, and deprivation by the lack of cognitive stimulation within the parent-child interaction. We used path analyses to test associations between deprivation and threat with psychopathology and school outcomes through cognition and emotional reactivity. We show that children who experienced more deprivation showed poor academic achievement through difficulties with executive function, while children who experienced more threat had higher levels of psychopathology through increased emotional reactivity. These observations are consistent with work in adolescence and reflect how unique adverse experiences have differential effects on children's behavior and subsequently long-term outcomes.

Life history in Caenorhabditis elegans: from molecular genetics to evolutionary ecology.

Life history is defined by traits that reflect key components of fitness, especially those relating to reproduction and survival. Research in life history seeks to unravel the relationships among these traits and understand how life history strategies evolve to maximize fitness. As such, life history research integrates the study of the genetic and developmental mechanisms underlying trait determination with the evolutionary and ecological context of Darwinian fitness. As a leading model organism for molecular and developmental genetics, Caenorhabditis elegans is unmatched in the characterization of life history-related processes, including developmental timing and plasticity, reproductive behaviors, sex determination, stress tolerance, and aging. Building on recent studies of natural populations and ecology, the combination of C. elegans' historical research strengths with new insights into trait variation now positions it as a uniquely valuable model for life history research. In this review, we summarize the contributions of C. elegans and related species to life history and its evolution. We begin by reviewing the key characteristics of C. elegans life history, with an emphasis on its distinctive reproductive strategies and notable life cycle plasticity. Next, we explore intraspecific variation in life history traits and its underlying genetic architecture. Finally, we provide an overview of how C. elegans has guided research on major life history transitions both within the genus Caenorhabditis and across the broader phylum Nematoda. While C. elegans is relatively new to life history research, significant progress has been made by leveraging its distinctive biological traits, establishing it as a highly cross-disciplinary system for life history studies.

Associations Between Developmental Stability, Canalization, and Phenotypic Plasticity in Response to Heterogeneous Experience.

The processes of developmental stability, canalization, and phenotypic plasticity have ecological and evolutionary significance, and been studied extensively, but mostly separately and thus the relationships between them are not straightforward. Our objective was to better integrate these processes in the context of temporally heterogeneous environments. We did this by investigating the effects of early experience with temporal heterogeneity in water availability on associations between developmental stability, canalization, and phenotypic plasticity. We subjected eight plant species to a first round of alternating inundation and drought vs. constantly moderate water treatments (heterogeneous experience) and a second round of water conditions (to test plasticity). We measured fluctuating asymmetry (FA) in leaf size, intra- and inter-individual variation (CVintra and CVinter), and plasticity (PI) in traits and analyzed correlations between these variables across all species. Results showed little correlations between FA, CVintra and PI, several positive correlations between FA and CVinter in more stressful conditions, especially in as well as positive correlations between CVinter and PI initially and negative correlations between them later. These suggested the complexity of these relationships, which can depend on whether plasticity occurs. Greater inter-individual variation will more likely cooperate with plasticity before or during plastic response, whereas higher canalization may reflect phenotypic convergence. Both higher FA and CVintra can reflect faster growth, while CVintra may also reflect plant growth stage, and the two mechanisms should cooperate in response to environmental challenges. The complexity of these relationships suggests plants deal with environmental variation in elaborate and integrative ways which can be affected by many factors.

Facilitation of Evolution by Plasticity Scales with Phenotypic Complexity

Developmental plasticity enables organisms to cope with new environmental challenges. If deploying such plasticity is costly in terms of time or energy, the same adaptive behaviour could subsequently evolve through piecemeal genomic reorganisation that replaces the requirement to acquire that adaptation by individual plasticity. Here, we report a new dimension to the way in which plasticity can drive evolutionary change, leading to an ever-greater complexity in biological organisation. Plasticity dramatically accelerates the evolutionary accumulation of adaptive systems in model organisms with relatively low rates of mutation. The effect of plasticity on the evolutionary growth of complexity is even greater when the number of elements needed to construct a functional system is increased. These results suggest that, as the difficulty of challenges from the environment becomes greater, plasticity exerts an ever more powerful role in meeting those challenges and in opening up new avenues for the subsequent evolution of complex adaptations.

ELONGATED HYPOCOTYL5-mediated light signaling promotes shoot regeneration in Arabidopsis thaliana.

Injured plant somatic tissues regenerate themselves by establishing shoot or root meristems. In Arabidopsis (Arabidopsis thaliana), a two-step culture system ensures regeneration by first promoting the acquisition of pluripotency and subsequently specifying the fate of new meristems. Although previous studies have reported the importance of phytohormones auxin and cytokinin in determining the fate of new meristems, whether and how environmental factors influence this process remains elusive. In this study, we investigated the impact of light signals on shoot regeneration using Arabidopsis hypocotyls as explants. We found that light signals promote shoot regeneration while inhibiting root formation. ELONGATED HYPOCOTYL 5 (HY5), the pivotal transcriptional factor in light signaling, plays a central role in this process by mediating the expression of key genes controlling the fate of new meristems. Specifically, HY5 directly represses root development genes and activates shoot meristem genes, leading to the establishment of shoot progenitor from pluripotent callus. We further demonstrated that the early activation of photosynthesis is critical for shoot initiation, and this is transcriptionally regulated downstream of HY5-dependent pathways. In conclusion, we uncovered the intricate molecular mechanisms by which light signals control the establishment of new meristems through the regulatory network governed by HY5, thus highlighting the influence of light signals on plant developmental plasticity.

The bifunctional transcription factor NAC32 modulates nickel toxicity responses through repression of root-nickel compartmentalization and activation of auxin biosynthesis

Nickel (Ni) is an important micronutrient, but excess Ni is toxic to many plant species. Currently, relatively little is known about the genetic basis of the plant responses to Ni toxicity. Here, we demonstrate that NAC32 transcription factor functions as a core genetic hub to regulate the Ni toxicity responses in Arabidopsis. NAC32 negatively regulates root-Ni concentration through the IREG2 (IRON REGULATED2) encoding a transporter. NAC32 also induces local auxin biosynthesis in the root-apex transition zone by upregulating YUCCA 7 (YUC7)/8/9 expression, which results in a local enhancement of auxin signaling in root tips, especially under Ni toxicity, thereby impaired primary root growth. By analyses of various combinations of nac32 and ireg2 mutants, as well as nac32 and yuc7/8/9 triple mutants, including high-order quadruple mutant, we demonstrated that NAC32 negatively regulates Ni stress tolerance by acting upstream of IREG2 and YUC7/8/9 to modulate their function in Ni toxicity responses. ChIPqPCR, EMSA (electrophoretic mobility shift assay) and transient dual-LUC reporter assays showed that NAC32 transcriptionally represses IREG2 expression but activates YUC7/8/9 expression by directly binding to their promoters. Our work demonstrates that NAC32 coordinates Ni compartmentation and developmental plasticity in roots, providing a conceptual framework for understanding Ni toxicity responses in plants.

Testing a Conceptual Model of Early Adversity, Neural Function, and Psychopathology: Protocol for a Retrospective Observational Cohort Study.

Early adversity, broadly defined as a set of negative exposures during childhood, is extremely common and increases risk for psychopathology across the life span. Previous research suggests that separate dimensions of adversity increase risk through developmental plasticity mechanisms shaping unique neurobiological pathways. Specifically, research suggests that deprivation is associated with deficits in higher order cognition, while threat is associated with atypicality in fear learning and emotion dysregulation. However, most of this research has been conducted in adolescent and adult samples, long after exposure to adversity occurs and far from periods of peak developmental plasticity. The Wellness Health and Life Experiences (WHALE) study examines the neurobiological and behavioral mechanisms by which deprivation, threat, and unpredictability increase risk for psychopathology in early childhood (age 4-7 years) directly following periods of peak developmental plasticity. The objective of this study is to describe the study rationale and aims, the research design and procedures, and the analytical plan to test the study hypotheses. This is a retrospective cohort study that examines associations between exposure to deprivation and threat and their hypothesized neurobiological mechanisms, how these neurobiological mechanisms link early adversity and psychopathology, and associations between unpredictability, reward learning, and psychopathology. The sample was a convenience sample of children (aged 4-7 years) and their families, identified through flyers, email blasts to listserves, school-based advertising, and involvement in community events. Data were collected during a home visit, a subsequent laboratory visit, and a final neuroimaging visit. Planned analyses include linear regression, path analyses, and functional magnetic resonance imaging analyses to explore the role of neural function in the association between early adversity and psychopathology. Participants (N=301) have been recruited into the study, and data collection has commenced. The expected results will be available in 2024. The findings of this study will help elucidate the neurobiological mechanisms by which early adversity increases risk for psychopathology in early childhood. This study represents the earliest test of an influential theory of biological embedding of early adversity. DERR1-10.2196/59636.

Developmental transcriptomics in Pristionchus reveals the logic of a plasticity gene regulatory network.

Developmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. While significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematode Pristionchus pacificus has culminated in 30 genes which affect mouth-form plasticity. We also recently reported the critical window of environmental sensitivity, and therefore have clear expectations for when differential gene expression should matter. Here, we collated previous data into a gene-regulatory network (GRN), and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mouth-form mutants to assess the regulatory logic of plasticity. We found that only two genes in the GRN (eud-1 and seud-1/sult-1) are sensitive to the environment during the critical window. Interestingly, the time points of their sensitivity differ, suggesting that they act as sequential checkpoints. We also observed temporal constraint upon the transcriptional effects of mutating the GRN and revealed unexpected feedback between mouth-form genes. Surprisingly, expression of seud-1/sult-1, but not eud-1, correlated with mouth form biases across different strains and species. Finally, a comprehensive analysis of all samples identified metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene-expression comparisons across development in up to 14 different conditions. Collectively, our results suggest that mouth-form plasticity evolved a constrained, two-tiered logic to integrate environmental information leading up to the final developmental decision.

Polarly localized Bro1 domain proteins regulate PIN-FORMED abundance and root gravitropic growth in Arabidopsis

The developmental plasticity of the root system plays an essential role in the adaptation of plants to the environment. Among many other signals, auxin and its directional, intercellular transport are critical in regulating root growth and development. In particular, the PIN-FORMED2 (PIN2) auxin exporter acts as a key regulator of root gravitropic growth. Multiple regulators have been reported to be involved in PIN2-mediated root growth; however, our information remains incomplete. Here, we identified ROWY Bro1-domain proteins as important regulators of PIN2 sorting control. Genetic analysis revealed that Arabidopsis rowy1 single mutants and higher-order rowy1 rowy2 rowy3 triple mutants presented a wavy root growth phenotype. Cell biological experiments revealed that ROWY1 and PIN2 colocalized to the apical side of the plasma membrane in the root epidermis and that ROWYs are required for correct PM targeting of PIN2. In addition, ROWYs also affected PIN3 protein abundance in the stele, suggesting the potential involvement of additional PIN transporters as well as other proteins. A global transcriptome analysis revealed that ROWY genes are involved in the Fe2+ availability perception pathway. This work establishes ROWYs as important novel regulators of root gravitropic growth by connecting micronutrient availability to the proper subcellular targeting of PIN auxin transporters.

Cold mediates maize root hair developmental plasticity via epidermis-specific transcriptomic responses.

Cold stress during early development limits maize (Zea mays L.) production in temperate zones. Low temperatures restrict root growth and reprogram gene expression. Here, we provide a systematic transcriptomic landscape of maize primary roots, their tissues, and cell types in response to cold stress. The epidermis exhibited a unique transcriptomic cold response, and genes involved in root hair formation were dynamically regulated in this cell type by cold. Consequently, activation of genes involved in root hair tip growth contributed to root hair recovery under moderate cold conditions. The maize root hair defective mutants roothair defective 5 (rth5) and roothair defective 6 (rth6) displayed enhanced cold tolerance with respect to primary root elongation. Furthermore, dehydration response element-binding protein 2.1 (dreb2.1) was the only member of the dreb subfamily of AP2/EREB transcription factor genes upregulated in primary root tissues and cell types but exclusively downregulated in root hairs upon cold stress. Plants overexpressing dreb2.1 significantly suppressed root hair elongation after moderate cold stress. Finally, the expression of rth3 was regulated by dreb2.1 under cold conditions, while rth6 transcription was regulated by dreb2.1 irrespective of the temperature regime. We demonstrated that dreb2.1 negatively regulates root hair plasticity at low temperatures by coordinating the expression of root hair defective genes in maize.

Breeding phenology drives variation in reproductive output, reproductive costs and offspring fitness in a viviparous ectotherm.

Phenological advances are a widespread response to global warming and can contribute to determine the climate vulnerability of organisms, particularly in ectothermic species which are highly dependent on ambient temperatures to complete their life cycle. Yet, the relative contribution of breeding dates and temperature conditions during gestation on fitness of females and their offspring is poorly documented in reptiles. Here, we exposed females of the common lizard Zootoca vivipara to contrasting thermal scenarios (cold versus hot treatment) during gestation and quantified effects of parturition dates and thermal treatment on life-history traits of females and their offspring for one year. Overall, our results suggest that parturition date has a greater impact than thermal conditions during gestation on life history strategies. In particular, we found positive effects of an earlier parturition date on juvenile survival, growth and recruitment suggesting that environmental dependent selection and/or differences in parental quality between early and late breeders underlie seasonal changes in offspring fitness. Yet, an earlier parturition date compromised the energetic condition of gravid females, which suggests the existence of a mother-offspring conflict regarding the optimisation of parturition dates. While numerous studies focused on the direct effects of alterations in incubation temperatures on reptile life-history traits, our results highlight the importance of considering the role of breeding phenology in assessing the short- and long-term effects of thermal developmental plasticity.

Persistent interactive effects of developmental salinity and temperature in Atlantic killifish (Fundulus heteroclitus)

Climate change alters multiple abiotic environmental factors in aquatic environments but relatively little is known about their interacting impacts, particularly in developing organisms where these exposures have the potential to cause long-lasting effects. To explore these issues, we exposed developing killifish embryos (Fundulus heteroclitus) to 26 °C or 20 °C and 20 ppt or 3 ppt salinity in a fully-factorial design. After hatching, fish were transferred to common conditions of 20 °C and 20 ppt to assess the potential for persistent developmental plasticity. Warm temperature increased hatching success and decreased hatch time, whereas low salinity negatively affected hatching success, but this was only significant in fish developed at 20 °C. Temperature, salinity, or their interaction affected mRNA levels of genes typically associated with thermal and hypoxia tolerance (hif1a, hsp90b, hsp90a, hsc70, and hsp70.2) across multiple developmental timepoints. These differences were persistent into the juvenile stage, where the fish that developed at 26 °C had higher expression of hif1a, hsp90b, hsp90a, and hsp70.2 than fish developed at 20 °C, and this was particularly evident for the group developed at both high temperature and salinity. There were also long-lasting effects of developmental treatments on body size after four months of rearing under common conditions. Fish developed at low salinity or temperature were larger than fish developed at high temperature or salinity, but there was no interaction between the two factors. These data highlight the complex nature of the developmental effects of interacting stressors which has important implications for predicting the resilience of fishes in the context of climate change.

Plasticity in older infants' perception of phonetic contrasts: The role of selective attention in context.

Developmental plasticity refers to conditions and circumstances that increase phenotypic variability. In infancy, plasticity expands and contracts depending on domains of functioning, developmental history, and timing. In terms of language processing, infants attend to and discriminate both native and non-native phonetic contrasts, but selectively attune to their native phonemes by the end of the first postnatal year. However, relevant studies have excluded factors regarded as promoters of attention such as infant-directed (ID) speech, synchronous multimodal presentations, and female speakers. Here we investigated whether English-learning 11-month-olds would discriminate a non-native phonetic contrast while manipulating these factors. Results showed significant discrimination of the non-native contrast, regardless of speech register, provided that they were presented by a dynamic female speaker. Interestingly, when a static object or a dynamic male ID speaker replaced the female, no significant discrimination was found. These results show infants to be capable of discriminating non-native phonetic contrasts in an enhanced context at an age when they have been characterized as not being able to do so. Synchronized, multimodal information from female speakers allowed infants to perceive difficult non-native phonemes, highlighting the importance of an ecologically valid context for studying speech perception and language learning in early development.

Minibrain plays a role in the adult brain development of honeybee (Apis mellifera) workers.

The brain of adult honeybee (Apis mellifera) workers is larger than that of queens, facilitating behavioural differentiation between the castes. This brain diphenism develops during the pharate-adult stage and is driven by a caste-specific gene expression cascade in response to unique hormonal milieus. Previous molecular screening identified minibrain (mnb; DYRK1A) as a potential regulator in this process. Here, we used RNAi approach to reduce mnb transcript levels and test its role on brain diphenism development in honeybees. White-eyed unpigmented cuticle worker pupae were injected with dsRNA for mnb (Mnb-i) or gfp, and their phenotypes were assessed two and 8 days later using classic histological and transcriptomic analyses. After 2 days of the injections, Mnb-i bees showed 98% of downregulation of mnb transcripts. After 8 days, the brain of Mnb-i bees showed reduction in total volume and in the volume of the mushroom bodies (MB), antennal, and optic lobes. Additionally, signs of apoptosis were observed in the Kenyon cells region of the MB, and the cohesion of the brain tissues was affected. Our transcriptomic analyses revealed that 226 genes were affected by the knockdown of mnb transcripts, most of which allowing axonal fasciculation. These results suggest the evolutionary conserved mnb gene has been co-opted for promoting hormone-mediated developmental brain morphological plasticity generating caste diphenism in honeybees.

Within the optimal thermal range, temperature fluctuations with similar means have little effect on offspring phenotypes: A comparison of two approaches that simulate natural nest conditions

Temperature influences nearly every aspect of organismal function. Because aspects of global change such as urbanization and climate change influence temperature, researchers must consider how altering thermal regimes will impact biodiversity across the planet. To do so, they often measure temperature in natural and/or human-modified habitats, replicate those temperatures in laboratory experiments to understand organismal responses, and make predictions under models of future change. Consequently, accurately representing temperature in the laboratory is an important concern, yet few studies have assessed the consequences of simulating thermal conditions in different ways. We used nest temperatures for two urban-dwelling, invasive lizards (Anolis sagrei and A. cristatellus) to create two egg incubation treatments in the laboratory. Like most studies of thermal developmental plasticity, we created daily repeating thermal fluctuations; however, we used different methods to create temperature treatments that differed in the magnitude and breadth of thermal cycles, and then evaluated the effects of these different approaches on embryo development and hatchling phenotypes. Additionally, we measured embryo heart rate, a proxy for metabolism, across temperature to understand the immediate effects of treatments. We found that treatments had minimal effect on phenotypes likely because temperatures were within the optimal thermal range for each species and were similar in mean temperature. We conclude that slight differences in thermal treatments may be unimportant so long as temperatures are within a range appropriate for development, and we make several recommendations for future studies of developmental plasticity.

Transcriptomic profiling reveals histone acetylation-regulated genes involved in somatic embryogenesis in Arabidopsis thaliana

BackgroundSomatic embryogenesis (SE) exemplifies the unique developmental plasticity of plant cells. The regulatory processes, including epigenetic modifications controlling embryogenic reprogramming of cell transcriptome, have just started to be revealed.ResultsTo identify the genes of histone acetylation-regulated expression in SE, we analyzed global transcriptomes of Arabidopsis explants undergoing embryogenic induction in response to treatment with histone deacetylase inhibitor, trichostatin A (TSA). The TSA-induced and auxin (2,4-dichlorophenoxyacetic acid; 2,4-D)-induced transcriptomes were compared. RNA-seq results revealed the similarities of the TSA- and auxin-induced transcriptomic responses that involve extensive deregulation, mostly repression, of the majority of genes. Within the differentially expressed genes (DEGs), we identified the master regulators (transcription factors - TFs) of SE, genes involved in biosynthesis, signaling, and polar transport of auxin and NITRILASE-encoding genes of the function in indole-3-acetic acid (IAA) biosynthesis. TSA-upregulated TF genes of essential functions in auxin-induced SE, included LEC1/LEC2, FUS3, AGL15, MYB118, PHB, PHV, PLTs, and WUS/WOXs. The TSA-induced transcriptome revealed also extensive upregulation of stress-related genes, including those related to stress hormone biosynthesis. In line with transcriptomic data, TSA-induced explants accumulated salicylic acid (SA) and abscisic acid (ABA), suggesting the role of histone acetylation (Hac) in regulating stress hormone-related responses during SE induction. Since mostly the adaxial side of cotyledon explant contributes to SE induction, we also identified organ polarity-related genes responding to TSA treatment, including AIL7/PLT7, RGE1, LBD18, 40, HB32, CBF1, and ULT2. Analysis of the relevant mutants supported the role of polarity-related genes in SE induction.ConclusionThe study results provide a step forward in deciphering the epigenetic network controlling embryogenic transition in somatic cells of plants.

Drivers of Intraspecific Variation in Thermal Traits and Their Importance for Resilience to Global Change in Amphibians.

Intraspecific variation can be as great as variation across species, but the role of intraspecific variation in driving local and large-scale patterns is often overlooked, particularly in the field of thermal biology. In amphibians, which depend on environmental conditions and behavior to regulate body temperature, recognizing intraspecific thermal trait variation is essential to comprehensively understanding how global change impacts populations. Here, we examine the drivers of micro- and macrogeographical intraspecific thermal trait variation in amphibians. At the local scale, intraspecific variation can arise via changes in ontogeny, body size, and between the sexes, and developmental plasticity, acclimation, and maternal effects may modulate predictions of amphibian performance under future climate scenarios. At the macrogeographic scale, local adaptation in thermal traits may occur along latitudinal and elevational gradients, with seasonality and range-edge dynamics likely playing important roles in patterns that may impact future persistence. We also discuss the importance of considering disease as a factor affecting intraspecific variation in thermal traits and population resilience to climate change, given the impact of pathogens on thermal preferences and critical thermal limits of hosts. Finally, we make recommendations for future work in this area. Ultimately, our goal is to demonstrate why it is important for researchers to consider intraspecific variation to determine the resilience of amphibians to global change.

Developmental plasticity of the cardiovascular system in oviparous vertebrates: effects of chronic hypoxia and interactive stressors in the context of climate change.

Animals at early life stages are generally more sensitive to environmental stress than adults. This is especially true of oviparous vertebrates that develop in variable environments with little or no parental care. These organisms regularly experience environmental fluctuations as part of their natural development, but climate change is increasing the frequency and intensity of these events. The developmental plasticity of oviparous vertebrates will therefore play a critical role in determining their future fitness and survival. In this Review, we discuss and compare the phenotypic consequences of chronic developmental hypoxia on the cardiovascular system of oviparous vertebrates. In particular, we focus on species-specific responses, critical windows, thresholds for responses and the interactive effects of other stressors, such as temperature and hypercapnia. Although important progress has been made, our Review identifies knowledge gaps that need to be addressed if we are to fully understand the impact of climate change on the developmental plasticity of the oviparous vertebrate cardiovascular system.

Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.