Functional Niche Research Articles

Abstract A066: Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs

Abstract Companion dogs have a lifetime cancer risk similar to that of humans. This excess risk, as compared to what is seen in other species, seems to be due to our recent success in outliving our evolutionarily adapted lifespan. For cancers to develop, a cancer-permissive environment must be present, which may exist months or even years before a tumor becomes detectable. We have developed the Shine On Suspicion (SOS) test; a flow cytometry based test to detect these changes that lead to a cancer-permissive environment. To make this test actionable, we combined it with eBAT, a novel bispecific ligand-targeted toxin that targets emerging cancer cells and the inflammatory niche to disrupt cancer formation. The Shine On Study used machine- learning algorithms to determine cancer risk based on a training set of 97 dogs with known conditions and a test set of 209 adult dogs with no evidence of cancer or other chronic diseases. Dogs assigned to the low-risk category had a less than 4% chance of developing cancer within 400 days after testing, whereas dogs assigned to the high-risk category had a nearly 25% chance of developing cancer in that timeframe. By 1,450 days, more than 50% of dogs assigned to the high-risk category developed cancer. Surprisingly, the SOS test’s specificity varied by breed. In Boxers and Portuguese Water Dogs the test accurately predicted the risk of hemangiosarcoma and other malignancies, whereas for Golden Retrievers, the test accurately predicted the risk for hemangiosarcoma, but no significant difference in the development of other cancers was observed between high-risk and low-risk groups. This suggests that the contribution of the cancer-permissive environment detected by the SOS test interacts with heritable factors, i.e., those defined by ancestry in creating the overall cancer risk state. To date, eBAT interception has been administered to 9 dogs, with only 1 potentially developing cancer 2 years after treatment. The drug is well-tolerated and shows promising outcomes. Future research aims to refine the SOS test, understand breed-specific responses, and explore the identity and function of niche- forming cells to improve cancer prevention strategies and their applicability to humans. Citation Format: Ashley J Schulte, Taylor A DePauw, Ali Khammanivong, Mitzi Lewellen, Lauren Burt, Rose Dicovitsky, Amber L Winter, Kathleen M Stuebner, Andrea Chehadeh, Sara Pracht, Christopher Ober, Kari L Anderson, Esther Nell, Antonella Borgatti, Michael S Henson, Erin B Dickerson, Aaron L Sarver, Daniel A Vallera, Gary R Cutter, Jaime F Modiano. Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A066.

Dietary amino acids, macronutrients, vaginal birth, and breastfeeding are associated with the vaginal microbiome in early pregnancy.

This secondary analysis of the MicrobeMom randomized controlled trial reveals that dietary amino acids, macronutrients, previous vaginal birth, and breastfeeding have the strongest associations with vaginal taxonomy in early pregnancy. Function of the vaginal niche is associated mainly by species composition, but smoking, vitamin K, and phenylalanine also play a role. These associations provide an intriguing and novel insight into the association between host factors and diet on the vaginal microbiome in pregnancy and highlight the need for further investigation into the complex interactions between the diet, human gut, and vaginal microbiome.

Lessons from long‐term research: Diptera species turnover and dominance shifts with respect to climate‐driven changes

Abstract The diverse pressures of climate change have influenced many habitats, especially freshwater ones, due to their greater sensitivity to stressors. Aquatic Diptera make up more than 50% off all aquatic insect species described, which makes them an ideal group to monitor changing climate as their diverse assemblages can reflect functions within the entire community. The aim of this research was to identify variations in the aquatic dipteran community during a 15‐year period at a tufa barrier in a karst barrage lake system and to determine the environmental factors that have the highest influence on this community. We analysed monthly data collected between 2007 and 2021, when we collected adult specimens using 6 pyramid‐type emergence traps. In total, 167 taxa from 13 different families were gathered. NMDS based on Bray–Curtis similarity analysis amongst assemblages revealed the segregation of samples based on different current velocities and substrates, indicating the importance of microhabitats in dipteran community structuring. Dipteran taxa indicative of specific 5‐year time periods within the research were identified and were associated with changes in environmental conditions especially discharge. The threshold indicator taxa analysis revealed specific species' responses to changing discharge rates. The study shows that discharge rate, not water temperature, is the critical factor shaping dipteran composition, whether by removing or adding taxa to the community. Species turnover showed an overall decrease in species numbers, that is, species richness, throughout the research period. We conclude that changes in the dipteran community, because of the vast functional traits, niches, adaptations and species diversity of the group, are not visible when analysing just the diversity indices. When determining environmental influence on the community in long‐term research, they should be combined with other data such as the overall abundance, the total number of species, as well as the species turnover.

Functional structure of the natural enemy community of the fall armyworm, Spodoptera frugiperda in the Americas

Ecosystem functions such as biological pest control are mediated by the richness and abundance of service providers i.e., biological control agents (BCAs), relative contributions of individual taxa and community structure. This is especially relevant in the native range of agricultural herbivores, where a speciose community of co-evolved BCAs can prevent them from attaining pest status. Here, we use a powerful graphical approach to assess the functional structure of BCA communities of the fall armyworm (FAW) Spodoptera frugiperda (Lepidoptera: Noctuidae) on maize in the Neotropics. Drawing upon a curated database of all-time field and laboratory studies, we graphed patterns in the functional contribution, abundance and niche breadth for a respective 69, 53 and 3 taxa of resident parasitoids, predators and pathogens. Regardless of varying taxon coverage and rigor of the underlying studies, functional structure follows a saturating relationship in which the first three taxa account for 90–98% of aggregate biological control function. Abundance-functionality matrices prove critically incomplete, as more than 80% of invertebrate taxa miss empirically derived efficiency metrics while associated FAW infestation data are scarce. Despite its methodological shortfalls and data gaps, our work pinpoints Chelonus insularis, several taxa of egg parasitoids, Doru spp. and Orius spp. as taxa with outsized (average) functionality and conservation potential. This is also exemplified by the highly variable aggregate function across studies, with dispersion indices of 1.52 and 2.14 for invertebrate BCAs. Our work underlines the critical importance of functional ecology research, networked trials and standardized methodologies in advancing conservation biological control globally.

The Drosophila hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling.

Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.

Seasonality Structures Avian Functional Diversity and Niche Packing Across North America.

Assemblages in seasonal ecosystems undergo striking changes in species composition and diversity across the annual cycle. Despite a long-standing recognition that seasonality structures biogeographic gradients in taxonomic diversity (e.g., species richness), our understanding of how seasonality structures other aspects of biodiversity (e.g., functional diversity) has lagged. Integrating seasonal species distributions with comprehensive data on key morphological traits for bird assemblages across North America, we find that seasonal turnover in functional diversity increases with the magnitude and predictability of seasonality. Furthermore, seasonal increases in bird species richness led to a denser packing of functional trait space, but functional expansion was important, especially in regions with higher seasonality. Our results suggest that the magnitude and predictability of seasonality and total productivity can explain the geography of changes in functional diversity with broader implications for understanding species redistribution, community assembly and ecosystem functioning.

Organic fertilizer significantly mitigates N2O emissions while increase contributed of comammox Nitrospira in paddy soils

Nitrification is the dominant process for nitrous oxide (N2O) production under aerobic conditions, but the relative contribution of the autotrophic nitrifiers (the ammonia-oxidising archaea (AOA), the ammonia-oxidising bacteria (AOB) and the comammox) to this process is still unclear in some soil types. This is particularly the case in paddy soils under different fertilization regimes. We investigated active nitrifiers and their contribution to nitrification and N2O production in a range of unfertilized and fertilized paddy soils, using 13CO2-DNA based stable isotope probing (SIP) technique combined with a series of specific nitrification inhibitors, including acetylene (C2H2), 3, 4-dimethylpyrazole phosphate (DMPP) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The soils had a long-term history of fertilizer application, including chemical fertilizer only, a mixture of chemical fertilizers (70 %) and chicken manure (30 %) or a mixture of rice straw and chemical fertilizers. 13CO2-DNA-SIP and Illumina MiSeq sequencing demonstrated that comammox clades A.1 and B were active nitrifiers in all fertilized paddy soils. Inhibitor experiment showed that AOB largely contributed to nitrification activity and N2O emission in all paddy soils, while comammox contribution was more significant than AOA. Fertilization considerably altered nitrifiers' relative contribution to nitrification activity and N2O emissions. Applying organic fertilizers significantly decreased the N2O emissions but increased the contribution of comammox to the process. These findings expand the functional ecological niche of comammox, revealing their nitrification role and N2O production in other ecosystems than oligotrophic habitats.

Eutrophication weakens the positive biodiversity–productivity relationship of benthic diatoms in plateau lakes

Context Freshwater primary productivity is threatened by the decline in biodiversity associated with nutrient enrichment, but there is still uncertainty about how the biodiversity and productivity relationship (BPR) varies with the trophic states. Aims We aimed to examine the variation of benthic diatom BPRs in three plateau lakes with different trophic states and their underlying driving mechanisms. Methods We examined the relationship between diatom taxonomic and functional diversity, niche width, and niche overlap with productivity. Key results The taxonomic and functional diversity, niche width and productivity of benthic diatoms were highest in the mesotrophic lake. The benthic diatom BPRs were linear and positive, with the slope of BPRs being the lowest in eutrophic lake. Motile, non-attached and small-sized diatoms were dominant in eutrophic lake. Nutrient concentrations indirectly affected primary productivity by influencing algal community structure, niche width and biodiversity change. Conclusions Diatom productivity and diversity showed a positive relationship, but nutrient enrichment weakened this relationship. By combining taxonomic and functional diversity indices, supplemented by niche analysis, we can further understand the variation of diatom productivity. Implications The results provide a basis for predicting the changes in BPRs of benthic diatoms in the littoral zone with different trophic states.

Glacier extinction homogenizes functional diversity via ecological succession

AbstractQuestionsThe disappearance of glaciers threatens biodiversity and the functioning of ecosystems. Yet, questions remain about the response of functional diversity to glacier retreat. How does glacier retreat influence functional diversity? How does glacier retreat influence the relationship between taxonomic diversity and functional diversity? How does glacier retreat impact community mean and intraspecific trait variability (ITV) of key functional traits?LocationFour retreating glacier ecosystems in the Italian Alps. Plant communities spanning 0 to ca 5000 years on average after glacier retreat, including a scenario of glacier extinction.MethodsWe quantified functional diversity analyzing twelve plant traits associated to carbon and nitrogen cycling, resource allocation, and reproduction of 117 plant species. We addressed how functional diversity changes with glacier retreat and taxonomic diversity (i.e., plant species richness).ResultsPlant functional diversity decreases with glacier extinction while increasing with species richness. The positive relationship between taxonomic and functional diversity becomes flatter, that is, less important, with glacier retreat. We document sharp changes in functional niche position and breadth with glacier retreat. Key functional traits associated with carbon cycling and resource allocation change substantially with ecological succession triggered by glacier retreat. Traits associated to nitrogen cycling show little change. We also found that flowering start shifted earlier in the season while flowering period increased with glacier retreat.ConclusionOur results demonstrate the pervasive impact of glacier extinction on the functioning of plant communities. Changes in functional mean and functional variation indicate shifts in niche position and niche breadth which could have implications for species adaptation to changing environments.

Is it all about size? Dismantling the integrated phenotype to understand species coexistence and niche segregation

Abstract Niche segregation is a mechanism by which competition between coexisting species is reduced. The ecological niche is a multidimensional space shaped by the conditions and resources that enable the existence of species. We conducted comprehensive univariate and multidimensional analyses of phenotypic traits encompassing morphology, functional performance and ecophysiology, to investigate which phenotypic traits contribute to niche segregation and overlap in two coexisting green lizard species. Our analyses revealed that the main driver of niche segregation was body size. However, when considering size‐corrected phenotypic spaces, ecophysiological traits were still distinct, with little overlap between co‐occurring species. Such differentiation was linked mainly to preferred temperature variance and water loss, highlighting the importance of thermal and hydric niche segregation. Some particular traits such as limb length also contributed to niche segregation being maintained in the morphological space, even when the effect of size was accounted for. Instead, the phenotypic space of functional performance traits (i.e. bite force, locomotor performance) showed the greatest overlap between the two species, thus, less niche segregation was observed, once size effects were removed. Therefore, functional performance traits contribute in a minor proportion to the effective niche segregation between the two species. In light of our results, the most adequate perspective to understand niche segregation in coexisting species is through a multidimensional approach in differentiated phenotypic spaces. Our dismantling of phenotypic traits allowed us to identify niche areas in which trait overlap occurs and others that promote niche segregation, considering or not size effects. Our results suggest that differential use of structural and functional niche space promotes effective niche segregation, potentially reducing direct competition between species. We highlight the importance of studies that include the combination of several phenotypic traits that, as a whole, provide insights to better understand the mechanisms by which coexisting organisms exploit differentiated resources in multidimensional spaces. Read the free Plain Language Summary for this article on the Journal blog.

Environmental influence on the functional ecological structure of benthic macrofaunal communities of the northwest Iberian coast

Evaluating the functional structure of benthic macrofaunal communities provides insights into how environmental drivers shape the ecosystem and establishes a baseline knowledge of the communities’ dynamics and functioning. This understanding allows the prediction of responses to environmental changes and the implementation of efficient conservation and management strategies. Here we examine the structures and functions of benthic macrofaunal communities on the Northwest Iberian coast concerning environmental factors such as depth, hydrodynamic energy, and bottom type. The results suggest that the community assemblages and their function are structured by factors which influence food availability and habitat heterogeneity. The different sites exhibited different trait compositions and functional structures, indicating that distinct functions are performed according to environmental conditions. The communities found in sandy bottom areas with low hydrodynamic conditions presented frail functionality and demonstrated high vulnerability to alterations in their environment. Conversely, the communities found in rocky bottoms with high hydrodynamic conditions exhibited a fulfilled functional niche space, rendering them more resilient to such changes and less prone to loss of function. Although the analyses did not reveal significant differences in the factor depth, its influence on several factors seems relevant in shaping the functional structure of the communities. These findings highlight the importance of understanding the impact of local environmental conditions on ecosystem functioning, to effectively implement monitoring, management, and conservation strategies.

The post-viral GPNMB+ immune niche persists in long-term Covid, asthma, and COPD.

Epithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.

Spatial diversity of in vivo tissue immunity.

The immune system exhibits spatial diversity in in vivo tissues. Immune cells are strategically distributed within tissues to maintain the organ integrity. Advanced technologies such as intravital imaging and spatial transcriptomics have revealed the spatial heterogeneity of immune cell distribution and function within organs such as the liver, kidney, intestine, and lung. In addition, these technologies visualize nutrient and oxygen environments across tissues. Recent spatial analyses have suggested that a functional immune niche is determined by interactions between immune and non-immune cells in an appropriate nutrient and oxygen environment. Understanding the spatial communication between immune cells, environment, and surrounding non-immune cells is crucial for developing strategies to control immune responses and effectively manage inflammatory diseases.

Functional redundancy and niche specialization in honeybee and Varroa microbiomes.

The honeybee (Apis mellifera) is a key pollinator critical to global agriculture, facing threats from various stressors, including the ectoparasitic Varroa mite (Varroa destructor). Previous studies have identified shared bacteria between Varroa mites and honeybees, yet it remains unclear if these bacteria assemble similarly in both species. This study builds on existing knowledge by investigating co-occurrence patterns in the microbiomes of both Varroa mites and honeybees, shedding light on potential interactions. Leveraging 16S rRNA datasets, we conducted co-occurrence network analyses, explored Core Association Networks (CAN) and assess network robustness. Comparative network analyses revealed structural differences between honeybee and mite microbiomes, along with shared core features and microbial motifs. The mite network exhibited lower robustness, suggesting less resistance to taxa extension compared to honeybees. Furthermore, analyses of predicted functional profiling and taxa contribution revealed that common central pathways in the metabolic networks have different taxa contributing to Varroa mites and honeybee microbiomes. The results show that while both microbial systems exhibit functional redundancy, in which different taxa contribute to the functional stability and resilience of the ecosystem, there is evidence for niche specialization resulting in unique contributions to specific pathways in each part of this host-parasite system. The specificity of taxa contribution to key pathways offers targeted approaches to Varroa microbiome management and preserving honeybee microbiome. Our findings provide valuable insights into microbial interactions, aiding farmers and beekeepers in maintaining healthy and resilient bee colonies amid increasing Varroa mite infestations.

An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells

Stem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed and how morphology impacts function. To address this, we leverage the Drosophila gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and non-muscle myosin II (MyoII) toward neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.

Effects of Ginsenoside Rb1 on the Crosstalk between Intestinal Stem Cells and Microbiota in a Simulated Weightlessness Mouse Model.

Exposure to the space microenvironment has been found to disrupt the homeostasis of intestinal epithelial cells and alter the composition of the microbiota. To investigate this in more detail and to examine the impact of ginsenoside Rb1, we utilized a mouse model of hindlimb unloading (HU) for four weeks to simulate the effects of microgravity. Our findings revealed that HU mice had ileum epithelial injury with a decrease in the number of intestinal stem cells (ISCs) and the level of cell proliferation. The niche functions for ISCs were also impaired in HU mice, including a reduction in Paneth cells and Wnt signaling, along with an increase in oxidative stress. The administration of Rb1 during the entire duration of HU alleviated the observed intestinal defects, suggesting its beneficial influence on epithelial cell homeostasis. Hindlimb unloading also resulted in gut dysbiosis. The supplementation of Rb1 in the HU mice or the addition of Rb1 derivative compound K in bacterial culture in vitro promoted the growth of beneficial probiotic species such as Akkermansia. The co-housing experiment further showed that Rb1 treatment in ground control mice alone could alleviate the defects in HU mice that were co-housed with Rb1-treated ground mice. Together, these results underscore a close relationship between dysbiosis and impaired ISC functions in the HU mouse model. It also highlights the beneficial effects of Rb1 in mitigating HU-induced epithelial injury by promoting the expansion of intestinal probiotics. These animal-based insights provide valuable knowledge for the development of improved approaches to maintaining ISC homeostasis in astronauts.

An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells.

Stem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed, and how morphology impacts function. To address this, we leverage the Drosophila gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad, and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and Non-muscle Myosin II (MyoII) towards neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells, and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.

A correctable immune niche for epithelial stem cell reprogramming and post-viral lung diseases.

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to the basal ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury.

Functional traits and ecological niches as correlates of the interspecific growth–mortality trade‐off among seedlings of 14 tropical tree species

Abstract The interspecific trade‐off between growth versus mortality rates of tree species is thought to be driven by functional biology and to contribute to species ecological niche differentiation. Yet, functional trait variation is often not strongly correlated with growth and mortality, and few studies have investigated the relationships of both traits and niches, specifically encompassing above and belowground resources, to the trade‐off itself. These relationships are particularly relevant for seedlings, which must often survive resource limitation to reach larger size classes. We investigated the functional basis of the interspecific growth–mortality trade‐off and its relationship with ecological niches for seedlings of 14 tree species in a tropical forest in southwest China. We found evidence for an interspecific growth–mortality trade‐off at the seedling stage using 15 functional traits and 15 ecological niche variables. None of the organ‐level traits correlated with growth, mortality, nor the trade‐off, whereas specific stem length (SSL), a biomass allocation trait, was the only trait to have a significant correlation (positive). Moreover, light‐defined niches were not correlated with growth, mortality or the trade‐off, but soil‐defined niches did. Species at the faster growth/higher mortality end of the trade‐off were associated with higher fertility defined by lower soil bulk density and slope, and higher soil organic matter concentration and soil total nitrogen. Our findings indicate the importance of stem elongation and soil fertility for growth, mortality and their trade‐off at the seedling stage in this Asian tropical forest. Our findings contrast with analogous studies in neotropical forests showing the importance of photosynthesis‐related leaf traits related to insolation. Therefore, the functional drivers of demographic rates and trade‐offs, as well as their consequences for ecological niches, can vary among forests, likely owing to differences in biogeography, canopy disturbance rates, topography and soil properties. Moreover, the effects of functional trait variation on demographic rates and trade‐offs may be better revealed when biomass allocation is accounted for in a whole‐plant context. Read the free Plain Language Summary for this article on the Journal blog.

REPRODUCTIVE AGEING: Altered histone modification landscapes underpin defects in uterine stromal cell decidualization in aging females.

Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females. Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated 'ground' state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.