Structural origin of relaxation in dense colloidal suspensions.

Amorphous solids relax via slow molecular rearrangement induced by thermal fluctuations or applied stress. Microscopic structural signatures predicting these structural relaxations have been long searched for but have so far only been found in dynamic quantities such as vibrational quasi-localized soft modes or with structurally trained neural networks. A physically meaningful structural quantity remains elusive. Here, we introduce a structural order parameter derived from the mean-field caging potential experienced by the particles due to their neighbors, which reliably predicts the occurrence of structural relaxations. The structural parameter, derived from density functional theory, provides a measure of susceptibility to particle rearrangements that can effectively identify weak or defect-like regions in disordered systems. Using experiments on dense colloidal suspensions, we demonstrate a strong correlation between this order parameter and the structural relaxations of the amorphous solid. In quiescent suspensions, this correlation increases with density, when particle rearrangements become rarer and more localized. In sheared suspensions, the order parameter reliably pinpoints shear transformations; the applied shear weakens the caging potential due to shear-induced structural distortions, causing the proliferation of plastic deformation at structurally weak regions. Our work paves the way to a structural understanding of the relaxation of a wide range of amorphous solids, from suspensions to metallic glasses.

Arthropod decline in grasslands and forests is associated with landscape-level drivers.

Recent reports of local extinctions of arthropod species1, and of massive declines in arthropod biomass2, point to land-use intensification as a major driver of decreasing biodiversity. However, to our knowledge, there are no multisite time series of arthropod occurrences across gradients of land-use intensity with which to confirm causal relationships. Moreover, it remains unclear which land-use types and arthropod groups are affected, and whether the observed declines in biomass and diversity are linked to one another. Here we analyse data from more than 1 million individual arthropods (about 2,700 species), from standardized inventories taken between 2008 and 2017 at 150 grassland and 140 forest sites in 3 regions of Germany. Overall gamma diversity in grasslands and forests decreased over time, indicating loss of species across sites and regions. In annually sampled grasslands, biomass, abundance and number of species declined by 67%, 78% and 34%, respectively. The decline was consistent across trophic levels and mainly affected rare species; its magnitude was independent of local land-use intensity. However, sites embedded in landscapes with a higher cover of agricultural land showed a stronger temporal decline. In 30 forest sites with annual inventories, biomass and species number-but not abundance-decreased by 41% and 36%, respectively. This was supported by analyses of all forest sites sampled in three-year intervals. The decline affected rare and abundant species, and trends differed across trophic levels. Our results show that there are widespread declines in arthropod biomass, abundance and the number of species across trophic levels. Arthropod declines in forests demonstrate that loss is not restricted to open habitats. Our results suggest that major drivers of arthropod decline act at larger spatial scales, and are (at least for grasslands) associated with agriculture at the landscape level. This implies that policies need to address the landscape scale to mitigate the negative effects of land-use practices.

Predictive modeling of oocyte maternal mRNA features for five mammalian species reveals potential shared and species-restricted regulators during maturation.

Oocyte maturation is accompanied by changes in abundances of thousands of mRNAs, many degraded and many preferentially stabilized. mRNA stability can be regulated by diverse features including GC content, codon bias, and motifs within the 3'-untranslated region (UTR) interacting with RNA binding proteins (RBPs) and miRNAs. Many studies have identified factors participating in mRNA splicing, bulk mRNA storage, and translational recruitment in mammalian oocytes, but the roles of potentially hundreds of expressed factors, how they regulate cohorts of thousands of mRNAs, and to what extent their functions are conserved across species has not been determined. We performed an extensive in silico cross-species analysis of features associated with mRNAs of different stability classes during oocyte maturation (stable, moderately degraded, and highly degraded) for five mammalian species. Using publicly available RNA sequencing data for germinal vesicle (GV) and MII oocyte transcriptomes, we determined that 3'-UTR length and synonymous codon usage are positively associated with stability, while greater GC content is negatively associated with stability. By applying machine learning and feature selection strategies, we identified RBPs and miRNAs that are predictive of mRNA stability, including some across multiple species and others more species-restricted. The results provide new insight into the mechanisms regulating maternal mRNA stabilization or degradation.NEW & NOTEWORTHY Conservation across species of mRNA features regulating maternal mRNA stability during mammalian oocyte maturation was analyzed. 3'-Untranslated region length and synonymous codon usage are positively associated with stability, while GC content is negatively associated. Just three RNA binding protein motifs were predicted to regulate mRNA stability across all five species examined, but associated pathways and functions are shared, indicating oocytes of different species arrive at comparable physiological destinations via different routes.

Dynamic changes in gene expression of growing nonhuman primate antral follicles.

The growth of the ovarian antral follicle is a complex process that is difficult to study, especially in human and nonhuman primates. Understanding the antral stage of development is key to new approaches to regulating reproduction. This study analyzed cohorts of three sizes of developing antral follicles obtained from adult rhesus macaque females using RNA sequencing of oocytes and cumulus and granulosa cells. The overall objective of this study was to identify key developmental changes in gene expression in oocytes, granulosa, and cumulus cells, as nonhuman primate antral stage follicles transition through progressively larger sizes in the absence of exogenous hormonal stimulation. Only a relatively small number of genes displayed altered mRNA expression levels in any of the three cell types during this period. Most of the identified differentially expressed genes (DEGs) decreased in the granulosa cells or increased in the cumulus cells. Although the number of DEGs observed was small, these DEGs indicate predicted effects on distinct upstream regulators in the cumulus and granulosa cells. This study is particularly important because it shows for the first time the gene expression changes during antral follicle growth in a medically relevant model.NEW & NOTEWORTHY Changes in gene expression in oocytes, granulosa, and cumulus cells were determined in nonhuman primate antral stage ovarian follicles transitioning through progressively larger sizes without exogenous hormonal stimulation. Only a small number of genes displayed altered mRNA expression levels in any of the three cell types. Most of the differentially expressed genes (DEGs) decreased in granulosa cells or increased in cumulus cells. These results identified upstream regulators of antral follicle development.

A map of canine sequence variation relative to a Greenland wolf outgroup.

For over 15 years, canine genetics research relied on a reference assembly from a Boxer breed dog named Tasha (i.e., canFam3.1). Recent advances in long-read sequencing and genome assembly have led to the development of numerous high-quality assemblies from diverse canines. These assemblies represent notable improvements in completeness, contiguity, and the representation of gene promoters and gene models. Although genome graph and pan-genome approaches have promise, most genetic analyses in canines rely upon the mapping of Illumina sequencing reads to a single reference. The Dog10K consortium, and others, have generated deep catalogs of genetic variation through an alignment of Illumina sequencing reads to a reference genome obtained from a German Shepherd Dog named Mischka (i.e., canFam4, UU_Cfam_GSD_1.0). However, alignment to a breed-derived genome may introduce bias in genotype calling across samples. Since the use of an outgroup reference genome may remove this effect, we have reprocessed 1929 samples analyzed by the Dog10K consortium using a Greenland wolf (mCanLor1.2) as the reference. We efficiently performed remapping and variant calling using a GPU-implementation of common analysis tools. The resulting call set removes the variability in genetic differences seen across samples and breed relationships revealed by principal component analysis are not affected by the choice of reference genome. Using this sequence data, we inferred the history of population sizes and found that village dog populations experienced a 9-13 fold reduction in historic effective population size relative to wolves.

Formation of mineral-associated organic matter in temperate soils is primarily controlled by mineral type and modified by land use and management intensity.

Formation of mineral-associated organic matter (MAOM) supports the accumulation and stabilization of carbon (C) in soil, and thus, is a key factor in the global C cycle. Little is known about the interplay of mineral type, land use and management intensity in MAOM formation, especially on subdecadal time scales. We exposed mineral containers with goethite or illite, the most abundant iron oxide and phyllosilicate clay in temperate soils, for 5 years in topsoils of 150 forest and 150 grassland sites in three regions across Germany. Results show that irrespective of land use and management intensity, more C accumulated on goethite than illite (on average 0.23 ± 0.10 and 0.06 ± 0.03 mg m-2 mineral surface respectively). Carbon accumulation across regions was consistently higher in coniferous forests than in deciduous forests and grasslands. Structural equation models further showed that thinning and harvesting reduced MAOM formation in forests. Formation of MAOM in grasslands was not affected by grazing. Fertilization had opposite effects on MAOM formation, with the positive effect being mediated by enhanced plant productivity and the negative effect by reduced plant species richness. This highlights the caveat of applying fertilizers as a strategy to increase soil C stocks in temperate grasslands. Overall, we demonstrate that the rate and amount of MAOM formation in soil is primarily driven by mineral type, and can be modulated by land use and management intensity even on subdecadal time scales. Our results suggest that temperate soils dominated by oxides have a higher capacity to accumulate and store C than those dominated by phyllosilicate clays, even under circumneutral pH conditions. Therefore, adopting land use and management practices that increase C inputs into oxide-rich soils that are under their capacity to store C may offer great potential to enhance near-term soil C sequestration.

Power-law intermittency in the gradient-induced self-propulsion of colloidal swimmers.

Active colloidal microswimmers serve as archetypical active fluid systems, and as models for biological swimmers. Here, by studying in detail their velocity traces, we find robust power-law intermittency with system-dependent exponential cut off. We model the intermittent motion by an interplay of the field gradient-dependent active force, which depends on a fluid gradient and is reduced when the swimmer moves, and the locally fluctuating hydrodynamic drag, that is set by the wetting properties of the substrate. The model closely describes the velocity distributions of two disparate swimmer systems: AC field activated and catalytic swimmers. The generality is highlighted by the collapse of all data in a single master curve, suggesting the applicability to further systems, both synthetic and biological.

Ovarian stimulation with excessive FSH doses causes cumulus cell and oocyte dysfunction in small ovarian reserve heifers.

Excessive FSH doses during ovarian stimulation in the small ovarian reserve heifer (SORH) cause premature cumulus expansion and follicular hyperstimulation dysgenesis (FHD) in nearly all ovulatory-size follicles with predicted disruptions in cell-signaling pathways in cumulus cells and oocytes (before ovulatory hCG stimulation). These observations support the hypothesis that excessive FSH dysregulates cumulus cell function and oocyte maturation. To test this hypothesis, we determined whether excessive FSH-induced differentially expressed genes (DEGs) in cumulus cells identified in our previously published transcriptome analysis were altered independent of extreme phenotypic differences observed amongst ovulatory-size follicles, and assessed predicted roles of these DEGs in cumulus and oocyte biology. We also determined if excessive FSH alters cumulus cell morphology, and oocyte nuclear maturation before (premature) or after an ovulatory hCG stimulus or during IVM. Excessive FSH doses increased expression of 17 cumulus DEGs with known roles in cumulus cell and oocyte functions (responsiveness to gonadotrophins, survival, expansion, and oocyte maturation). Excessive FSH also induced premature cumulus expansion and oocyte maturation but inhibited cumulus expansion and oocyte maturation post-hCG and diminished the ability of oocytes with prematurely expanded cumulus cells to undergo IVF or nuclear maturation during IVM. Ovarian stimulation with excessive FSH is concluded to disrupt cumulus cell and oocyte functions by inducing premature cumulus expansion and dysregulating oocyte maturation without an ovulatory hCG stimulus yielding poor-quality cumulus-oocyte complexes that may be incorrectly judged morphologically as suitable for IVF during ART.

Self-Oscillation and Synchronization Transitions in Elastoactive Structures.

The interplay between activity and elasticity often found in active and living systems triggers a plethora of autonomous behaviors ranging from self-assembly and collective motion to actuation. Among these, spontaneous self-oscillations of mechanical structures is perhaps the simplest and most widespread type of nonequilibrium phenomenon. Yet, we lack experimental model systems to investigate the various dynamical phenomena that may appear. Here, we introduce a centimeter-sized model system for one-dimensional elastoactive structures. We show that such structures exhibit flagellar motion when pinned at one end, self-snapping when pinned at two ends, and synchronization when coupled together with a sufficiently stiff link. We further demonstrate that these transitions can be described quantitatively by simple models of coupled pendula with follower forces. Beyond the canonical case considered here, we anticipate our work to open avenues for the understanding and design of the self-organization and response of active biological and synthetic solids, e.g., in higher dimensions and for more intricate geometries.

Controlled Assembly of CdSe Nanoplatelet Thin Films and Nanowires.

We assemble semiconductor CdSe nanoplatelets (NPs) at the air/liquid interface into 2D monolayers several micrometers wide, distinctly displaying nematic order. We show that this configuration is the most favorable energetically and that the edge-to-edge distance between neighboring NPs can be tuned by ligand exchange without disrupting film topology and nanoparticle orientation. We explore the rich assembly phase space by using depletion interactions to direct the formation of 1D nanowires from stacks of NPs. The improved control and understanding of the assembly of semiconductor NPs offers opportunities for the development of cheaper optoelectronic devices that rely on 1D or 2D charge delocalization throughout the assembled monolayers and nanowires.

Phases of surface-confined trivalent colloidal particles.

Patchy colloids promise the design and modelling of complex materials, but the realization of equilibrium patchy particle structures remains challenging. Here, we assemble pseudo-trivalent particles and elucidate their phase behaviour when confined to a plane. We observe the honeycomb phase, as well as more complex amorphous network and triangular phases. Structural analysis performed on the three condensed phases reveals their shared structural motifs. Using a combined experimental and simulation approach, we elucidate the energetics of these phases and construct the phase diagram of this system, using order parameters to determine the phase coexistence lines. Our results reveal the rich phase behaviour that a relatively simple patchy particle system can display, and open the door to a larger joined simulation and experimental exploration of the full patchy-particle phase space.

Land-use intensity alters networks between biodiversity, ecosystem functions, and services.

Land-use intensification can increase provisioning ecosystem services, such as food and timber production, but it also drives changes in ecosystem functioning and biodiversity loss, which may ultimately compromise human wellbeing. To understand how changes in land-use intensity affect the relationships between biodiversity, ecosystem functions, and services, we built networks from correlations between the species richness of 16 trophic groups, 10 ecosystem functions, and 15 ecosystem services. We evaluated how the properties of these networks varied across land-use intensity gradients for 150 forests and 150 grasslands. Land-use intensity significantly affected network structure in both habitats. Changes in connectance were larger in forests, while changes in modularity and evenness were more evident in grasslands. Our results show that increasing land-use intensity leads to more homogeneous networks with less integration within modules in both habitats, driven by the belowground compartment in grasslands, while forest responses to land management were more complex. Land-use intensity strongly altered hub identity and module composition in both habitats, showing that the positive correlations of provisioning services with biodiversity and ecosystem functions found at low land-use intensity levels, decline at higher intensity levels. Our approach provides a comprehensive view of the relationships between multiple components of biodiversity, ecosystem functions, and ecosystem services and how they respond to land use. This can be used to identify overall changes in the ecosystem, to derive mechanistic hypotheses, and it can be readily applied to further global change drivers.

Late-spring frost risk between 1959 and 2017 decreased in North America but increased in Europe and Asia.

Late-spring frosts (LSFs) affect the performance of plants and animals across the world's temperate and boreal zones, but despite their ecological and economic impact on agriculture and forestry, the geographic distribution and evolutionary impact of these frost events are poorly understood. Here, we analyze LSFs between 1959 and 2017 and the resistance strategies of Northern Hemisphere woody species to infer trees' adaptations for minimizing frost damage to their leaves and to forecast forest vulnerability under the ongoing changes in frost frequencies. Trait values on leaf-out and leaf-freezing resistance come from up to 1,500 temperate and boreal woody species cultivated in common gardens. We find that areas in which LSFs are common, such as eastern North America, harbor tree species with cautious (late-leafing) leaf-out strategies. Areas in which LSFs used to be unlikely, such as broad-leaved forests and shrublands in Europe and Asia, instead harbor opportunistic tree species (quickly reacting to warming air temperatures). LSFs in the latter regions are currently increasing, and given species' innate resistance strategies, we estimate that ∼35% of the European and ∼26% of the Asian temperate forest area, but only ∼10% of the North American, will experience increasing late-frost damage in the future. Our findings reveal region-specific changes in the spring-frost risk that can inform decision-making in land management, forestry, agriculture, and insurance policy.

A New Role for SMCHD1 in Life's Master Switch and Beyond.

Structural maintenance of chromosomes flexible hinge-domain containing protein 1 (SMCHD1) has emerged as a key regulator of embryonic genome function. Its functions have now extended well beyond the initial findings of effects on X chromosome inactivation associated with lethality in female embryos homozygous for a null allele. Autosomal dominant effects impact stem cell properties as well as postnatal health. Recent studies have revealed that SMCHD1 plays an important role as a maternal effect gene that regulates the master switch of life, namely embryonic genome activation, as well as subsequent preimplantation development and term viability. These discoveries mark SMCHD1 as a major regulator linking developmental processes to adult disorders including a form of muscular dystrophy.

Negative effects of forest gaps on dung removal in a full-factorial experiment.

Ecosystem functioning may directly or indirectly-via change in biodiversity-respond to land use. Dung removal is an important ecosystem function central for the decomposition of mammal faeces, including secondary seed dispersal and improved soil quality. Removal usually increases with dung beetle diversity and biomass. In forests, dung removal can vary with structural variables that are, however, often interrelated, making experiments necessary to understand the role of single variables on ecosystem functions. How gaps and deadwood, two main outcomes of forest management influence dung removal, is unknown. We tested if dung removal responds to gap creation and deadwood provisioning or if treatment effects are mediated via responses of dung beetles. We expected lower removal rates in gaps due to lower dung beetle biomass and diversity. We sampled dung beetles and measured dung removal in a highly-replicated full-factorial forest experiment established at 29 sites in three regions of Germany (treatments: Gap, Gap + Deadwood, Deadwood, Control). All gaps were experimentally created and had a diameter of around 30 m. Dung beetle diversity, biomass and dung removal were each lower in gaps than in controls. Dung removal decreased from 61.9% in controls to 48.5% in gaps, irrespective of whether or not the gap had deadwood. This treatment effect was primarily driven by dung beetle biomass but not diversity. Furthermore, dung removal was reduced to 56.9% in the deadwood treatment. Our findings are not consistent with complementarity effects of different dung beetle species linked to biodiversity-ecosystem functioning relationships that have been shown in several ecosystems. In contrast, identity effects can be pronounced: gaps reduced the abundance of a large-bodied key forest species (Anoplotrupes stercorosus), without compensatory recruitment of open land species. While gaps and deadwood are important for many forest organisms, dung beetles and dung removal respond negatively. Our results exemplify how experiments can contribute to test hypotheses on the interrelation between land use, biodiversity and ecosystem functioning.

Land-use intensification causes multitrophic homogenization of grassland communities.

Land-use intensification is a major driver of biodiversity loss. Alongside reductions in local species diversity, biotic homogenization at larger spatial scales is of great concern for conservation. Biotic homogenization means a decrease in ß-diversity (the compositional dissimilarity between sites). Most studies have investigated losses in local (α)-diversity and neglected biodiversity loss at larger spatial scales. Studies addressing ß-diversity have focused on single or a few organism groups (for example, ref. 4), and it is thus unknown whether land-use intensification homogenizes communities at different trophic levels, above- and belowground. Here we show that even moderate increases in local land-use intensity (LUI) cause biotic homogenization across microbial, plant and animal groups, both above- and belowground, and that this is largely independent of changes in α-diversity. We analysed a unique grassland biodiversity dataset, with abundances of more than 4,000 species belonging to 12 trophic groups. LUI, and, in particular, high mowing intensity, had consistent effects on ß-diversity across groups, causing a homogenization of soil microbial, fungal pathogen, plant and arthropod communities. These effects were nonlinear and the strongest declines in ß-diversity occurred in the transition from extensively managed to intermediate intensity grassland. LUI tended to reduce local α-diversity in aboveground groups, whereas the α-diversity increased in belowground groups. Correlations between the ß-diversity of different groups, particularly between plants and their consumers, became weaker at high LUI. This suggests a loss of specialist species and is further evidence for biotic homogenization. The consistently negative effects of LUI on landscape-scale biodiversity underscore the high value of extensively managed grasslands for conserving multitrophic biodiversity and ecosystem service provision. Indeed, biotic homogenization rather than local diversity loss could prove to be the most substantial consequence of land-use intensification.

Effects of early lactation body condition loss in dairy cows on serum lipid profiles and on oocyte and cumulus cell transcriptomes.

The objective of this study was to determine the effect of early lactation body condition (BC) loss in multiparous dairy cows on serum lipids and the effect of these changes on oocyte and cumulus cell transcriptomes. Body condition loss in dairy cattle after parturition is associated with reduced fertility and increased pregnancy loss. The complex interplay between BC, nutrition, dry matter intake, milk production, and time of calving has presented a barrier to understanding mechanisms leading to reduced fertility. We identified cows that lost BC (L group; n = 10) or maintained or gained BC (M/G group; n = 8) during the first 27 to 33 d in milk and investigated changes in serum fatty acids and oocyte and cumulus cell transcriptomes at 75 to 81 d in milk. The L group had increased serum levels of nonesterified fatty acids and mead acid, and reduced serum levels of petroselaidic acid and behenic acid. Transcriptome analyses revealed 38 differentially expressed genes (DEG) in oocytes and 71 DEG in cumulus cells of L (n = 3) compared with M/G group (n = 3). Network analysis connected serum fatty acid changes to downstream effects including reduced inflammatory response and mitochondrial membrane depolarization, increased production of reactive oxygen species, and functions related to fatty acid metabolism and cytoplasmic organization in oocytes. These effects were associated with predicted effects on signaling in oocytes through calcium, insulin, O-GlcNAcase (OGA), fibroblast growth factor receptor 4 (FGF4R), peroxisome proliferator activated receptor gamma coactivator 1 α (PPARGC1A), and phospholipase D2 (PLD2) pathways, with a connection to the cumulus cell via calcium signaling. These results connect BC loss following parturition to changes in serum lipid levels, and changes potentially affecting oocyte quality; thus, these results provide new insight into mechanism of reduced fertility.

Essential shared and species-specific features of mammalian oocyte maturation-associated transcriptome changes impacting oocyte physiology.

Oogenesis is a complex process resulting in the production of a truly remarkable cell-the oocyte. Oocytes execute many unique processes and functions such as meiotic segregation of maternal genetic material, and essential life-generating functions after fertilization including posttranscriptional support of essential homeostatic and metabolic processes, and activation and reprogramming of the embryonic genome. An essential goal for understanding female fertility and infertility in mammals is to discover critical features driving the production of quality oocytes, particularly the complex regulation of oocyte maternal mRNAs. We report here the first in-depth meta-analysis of oocyte maturation-associated transcriptome changes, using eight datasets encompassing 94 RNAseq libraries for human, rhesus monkey, mouse, and cow. A majority of maternal mRNAs are regulated in a species-restricted manner, highlighting considerable divergence in oocyte transcriptome handling during maturation. We identified 121 mRNAs changing in relative abundance similarly across all four species (92 of high homology), and 993 (670 high homology) mRNAs regulated similarly in at least three of the four species, corresponding to just 0.84% and 6.9% of mRNAs analyzed. Ingenuity Pathway Analysis (IPA) revealed an association of these shared mRNAs with many shared pathways and functions, most prominently oxidative phosphorylation and mitochondrial function. These shared functions were reinforced further by primate-specific and species-specific differentially expressed genes (DEGs). Thus, correct downregulation of mRNAs related to oxidative phosphorylation and mitochondrial function is a major shared feature of mammalian oocyte maturation.

Cross-species meta-analysis of transcriptome changes during the morula-to-blastocyst transition: metabolic and physiological changes take center stage.

The morula-to-blastocyst transition (MBT) culminates with formation of inner cell mass (ICM) and trophectoderm (TE) lineages. Recent studies identified signaling pathways driving lineage specification, but some features of these pathways display significant species divergence. To better understand evolutionary conservation of the MBT, we completed a meta-analysis of RNA sequencing data from five model species and ICMTE differences from four species. Although many genes change in expression during the MBT within any given species, the number of shared differentially expressed genes (DEGs) is comparatively small, and the number of shared ICMTE DEGs is even smaller. DEGs related to known lineage determining pathways (e.g., POU5F1) are seen, but the most prominent pathways and functions associated with shared DEGs or shared across individual species DEG lists impact basic physiological and metabolic activities, such as TCA cycle, unfolded protein response, oxidative phosphorylation, sirtuin signaling, mitotic roles of polo-like kinases, NRF2-mediated oxidative stress, estrogen receptor signaling, apoptosis, necrosis, lipid and fatty acid metabolism, cholesterol biosynthesis, endocytosis, AMPK signaling, homeostasis, transcription, and cell death. We also observed prominent differences in transcriptome regulation between ungulates and nonungulates, particularly for ICM- and TE-enhanced mRNAs. These results extend our understanding of shared mechanisms of the MBT and formation of the ICM and TE and should better inform the selection of model species for particular applications.

Shared aspects of mRNA expression associated with oocyte maturation failure in humans and rhesus monkeys indicating compromised oocyte quality.

Oocyte maturation failure observed in assisted reproduction technology (ART) cycles can limit the number of quality oocytes obtained and present a pronounced barrier for some patients. The potential exists to use unmatured oocytes for ART through in vitro maturation. Understanding the molecular basis of oocyte maturation failure is pertinent to minimizing this loss of oocytes and considerations of whether such oocytes can be used safely for ART. We identified shared transcriptome abnormalities for rhesus monkey and human failed-to-mature (FTM) oocytes relative to healthy matured MII stage oocytes. We discovered that, although the number of shared affected genes was comparatively small, FTM oocytes in both species shared effects for several pathways and functions, including predicted activation of oxidative phosphorylation (OxPhos) with additional effects on mitochondrial function, lipid metabolism, transcription, nucleotide excision repair, endoplasmic reticulum stress, unfolded protein response, and cell viability. RICTOR emerged as a prominent upstream regulator with predicted inhibition across all analyses. Alterations in KDM5A, MTOR, MTORC1, INSR, CAB39L, and STK11 activities were implicated along with RICTOR in modulating mitochondrial activity and OxPhos. Defects in cell cycle progression were not a prominent feature of FTM oocytes. These results identify a common set of transcriptome abnormalities associated with oocyte maturation failure. While our results do not demonstrate causality, they indicate that fundamental aspects of cellular function are abnormal in FTM oocytes and raise significant concerns about the potential risks of using FTM oocytes for ART.