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Universality and flexibility in gene expression from bacteria to human.

Highly parallel experimental biology is offering opportunities to not just accomplish work more easily, but to explore for underlying governing principles. Recent analysis of the large-scale organization of gene expression has revealed its complex and dynamic nature. However, the underlying dynamics that generate complex gene expression and cellular organization are not yet understood. To comprehensively and quantitatively elucidate these underlying gene expression dynamics, we have analyzed genome-wide gene expression in many experimental conditions in Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster, Mus musculus, and Homo sapiens. Here we demonstrate that the gene expression dynamics follows the same and surprisingly simple principle from E. coli to human, where gene expression changes are proportional to their expression levels, and show that this "proportional" dynamics or "rich-travel-more" mechanism can regenerate the observed complex and dynamic organization of the transcriptome. These findings provide a universal principle in the regulation of gene expression, show how complex and dynamic organization can emerge from simple underlying dynamics, and demonstrate the flexibility of transcription across a wide range of expression levels.

Animals↗

Dynamic effects of short-term storage temperature and duration on the transcriptome and functional pathways of umbilical cord blood-derived NK cells.

OBJECTIVE: This study aims to elucidate the dynamic impact of different storage conditions (temperature and time) on the function of natural killer (NK) cells derived from umbilical cord blood (UCB) at the transcriptome level, providing a theoretical basis for optimizing the standardized post-collection processing protocol of UCB in clinical settings. METHODS: Four healthy full-term UCB samples were collected and assigned to a fresh control group (0H) and experimental groups stored at 4 °C (4C) or 25 °C (RT) for 24 h (24H) and 72 h (72H). Umbilical cord blood mononuclear cells (CBMCs) were isolated and expanded in vitro to derive NK cells. Using RNA sequencing (RNA-seq) technology, combined with principal component analysis (PCA), screening of differentially expressed genes (DEGs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the effects of storage conditions on the transcriptome of NK cells were comprehensively analyzed. RESULTS: The results indicated that storage time was the primary factor causing transcriptomic differences. Compared to the 0H group, storage for 24 h induced a limited number of Differentially Expressed Genes (DEGs) (only 11 in the 24H-RT group), indicating overall transcriptome stability. In contrast, storage for 72 h triggered profound transcriptomic reprogramming, with DEGs significantly enriched in immune activation-related pathways. Specifically, at the 72-h time point, storage at 4 °C compared to 25 °C prevented the downregulation of key metabolic pathways such as 'response to decreased oxygen levels' and 'regulation of leukocyte cell-cell adhesion'. CONCLUSION: CBMC-derived NK cells can tolerate up to 24 h of ex vivo storage while maintaining transcriptome and core functional stability. However, extending the ex vivo storage period to 72 h leads to significant reprogramming in the expression of immune and metabolism-related genes. Notably, the degree of metabolic suppression under refrigerated conditions at 4 °C was less pronounced than that at 25 °C room temperature storage. This study recommends that the ex vivo storage time of UCB should ideally be limited to within 24 h, with room temperature storage being a viable option. If prolonged storage is necessary, refrigeration at 4 °C is advised.

Humans↗

Charting Postnatal Heart Development Using In Vivo Single-Cell Functional Genomics.

The transition at birth, marked by increased circulatory demands and rapid growth, necessitates extensive remodeling of the heart's structure, function, and metabolism. This transformation requires precise spatial and temporal coordination among diverse cardiac cell types; central to this process is cardiomyocyte maturation, yet the regulatory mechanisms driving these changes remain poorly understood. Here, we present a temporal and spatial atlas of postnatal hearts by integrating single-nucleus transcriptomics with image-based spatial transcriptomics, which uncovers the dynamic regulatory networks of cardiomyocyte maturation. To functionally interrogate candidate regulators in vivo , we developed Probe-based Indel-detectable Perturb-seq (PIP-seq), a high-throughput platform that uses probe-based chemistry to directly capture sgRNA expression, perturbation status, and transcriptomic profiles at single-nucleus resolution. Applying PIP-seq to postnatal cardiac development identified 21 novel regulators of cardiomyocyte maturation, highlighting critical nodal points in this process. Our study establishes a high-resolution framework for dissecting postnatal heart development, underscoring the integrative and highly ordered roles of microenvironment and intercellular communication in cardiomyocyte maturation. Importantly, PIP-seq enables systematic, high-throughput exploration of gene function and networks underlying complex biological processes in their native in vivo context.

Journal Article↗

Genomic, transcriptomic, and molecular predictors of response to neoadjuvant therapy in locally advanced rectal cancer: a narrative review.

Total neoadjuvant therapy (TNT) has emerged as a key treatment paradigm for locally advanced rectal cancer, reducing distant metastasis rates and facilitating organ preservation in selected patients. However, treatment response remains heterogeneous, highlighting the need for biomarkers that can guide treatment selection and optimise outcomes. This narrative review synthesises the current evidence regarding tumour-intrinsic genomic biomarkers associated with response to neoadjuvant therapy, encompassing somatic mutations, germline polymorphisms, gene expression profiles, mismatch repair (MMR) status, protein expression, epigenetic markers, and circulating tumour-derived biomarkers across conventional chemoradiotherapy (CRT) and TNT paradigms. Across the reviewed literature, individual somatic mutations, including KRAS, TP53, and BRAF, demonstrated limited reproducibility as predictive biomarkers, although KRAS mutations were recurrently associated with lower pathological complete response (pCR) rates in CRT-era cohorts. Germline polymorphisms in DNA repair (XRCC1) and folate metabolism (MTHFR) genes showed inconsistent associations with treatment response. In contrast, transcriptomic biomarkers demonstrated greater biological coherence, with proliferative, epithelial-mesenchymal transition, and metabolic signatures frequently associated with treatment resistance, while multi-gene classifiers generally outperformed single-gene markers. Among currently available tumour-intrinsic biomarkers, MMR deficiency was the most consistently reported biomarker associated with reduced response to fluoropyrimidine-based regimens, including TNT, although TNT-specific evidence remains comparatively limited. Dynamic circulating tumour DNA (ctDNA) monitoring, particularly ctDNA clearance during or after therapy, was consistently associated with pathological response and long-term oncologic outcomes across reviewed studies, whereas baseline ctDNA levels showed limited predictive value. Overall, the reviewed literature suggests that biomarker research in rectal cancer has evolved from single-gene analyses towards pathway-level and dynamic biomarkers. The integration of transcriptomic signatures, MMR status, and dynamic ctDNA monitoring may represent a promising strategy for personalising neoadjuvant therapy, improving patient selection for organ-preserving approaches, and enhancing oncologic outcomes in locally advanced rectal cancer. Nevertheless, the evidence base remains heterogeneous, and further prospective validation, assay standardisation, and evaluation within contemporary TNT cohorts are required before these biomarkers can be routinely incorporated into clinical decision-making.

Humans↗

Transcriptional regulation of cardiac progenitor cell populations.

Transcriptome-wide analysis of dynamically regulated progenitor cell populations has the potential to elucidate key aspects of cardiac development. The heart, as the first organ to develop in the mammal, is a technically challenging but clinically relevant target for study. To define the transcriptional program of the cardiac progenitor, we used a novel transgenic strategy and fluorescence-activated cell sorting to reliably label and isolate cardiac progenitors directly from mouse embryos. Pure populations of cardiac progenitor cells were isolated from the cardiac crescent and 2 subsequent stages of heart development: the linear heart tube and the looping heart. RNA was isolated from stage-specific cardiac progenitors and subjected to transcriptome analysis by oligonucleotide array hybridization. The cardiac transcriptional regulatory programs were compared with the molecular programs of age-matched noncardiac embryonic cells, embryonic stem cells, adult cardiomyocytes, and each other to identify sets of genes exhibiting differential expression in the cardiac progenitor cell population. These results define the transcriptional profile of mammalian cardiac progenitor cells and provide insight into the molecular regulation of the earliest periods of heart development.

Animals↗

Spatially guided in vivo single-cell functional genomics of postnatal heart.

Understanding how spatial organization and cell-cell interactions shape gene regulatory programs is central to decoding tissue development and function. The transition at birth, marked by increased circulatory demands and rapid tissue growth, requires precise spatiotemporal coordination of cardiac maturation. In this study, we generated a high-resolution spatial and temporal atlas of the postnatal mouse heart by integrating single-nucleus RNA sequencing with image-based spatial transcriptomics. This framework revealed dynamic cellular interactions, niche-specific signaling and transcriptional programs guiding cardiomyocyte maturation. To functionally test prioritized regulators in vivo and at scale, we developed PIP-seq (probe-based indel-detectable Perturb-seq), a high-throughput platform that detects single guide RNA identity, infers gene editing and profiles transcription from fixed nuclei. Applying PIP-seq to the developing postnatal heart, we identified 21 previously uncharacterized regulators of cardiomyocyte maturation, including genes essential for sarcomere assembly, metabolic reprogramming and electrophysiological transitions. Together, our findings define how microenvironmental signals and intrinsic gene programs cooperate to guide heart maturation and establish a broadly applicable framework for functional genomics in complex tissues.

Animals↗

Transcriptome profiling of the tubular porcine conceptus identifies the differential regulation of growth and developmentally associated genes.

Gastrulation and trophectoderm elongation of the porcine conceptus coincide with peak conceptus estrogen secretion from gestational day 11 to day 12. The current study aim was to identify genes required for elongation by defining the transcriptome profile of this dynamic tubular stage. The gastrulation and proliferative status of ovoid, tubular, and filamentous conceptuses were also examined. Polarization of the embryonic disc and growth throughout the conceptus were evident. An unamplified and two distinct amplified serial analysis of gene expression (SAGE) libraries were generated from tubular conceptus mRNA. Comparing the three libraries at 12,000 tags/library indicated small-amplified RNA-SAGE was a reliable amplification procedure. The unamplified library was increased to 42,415 tags and statistical analyses of tag frequencies with previously generated ovoid and filamentous libraries revealed the differential expression (P < 0.05) of 483 and 364 tags between ovoid:tubular or tubular:filamentous libraries, respectively. Annotated transcripts known to be involved in development and also potentially regulated by estrogen (cytokeratins 8 and 18, stratifin, midkine, and glycolytic enzymes) were further analyzed by real-time PCR. The majority of glycolytic enzyme transcripts were constitutively expressed or downregulated at the filamentous stage. Likewise, cytokeratin mRNAs were less abundant in filamentous conceptuses, whereas stratifin and midkine were more abundant in tubular conceptuses. Analysis of protein revealed distinct expression patterns for cytokeratin 18, stratifin, and midkine. The function(s) of these factors and potential modulation by estrogen clearly needs to be elucidated to understand their physiological role in normal conceptus development.

Animals↗

A quantitative and validated SAGE transcriptome reference for adult mouse heart.

Transcriptome comparisons facilitate the identification of developmental, aging, and disease-related genes. To quantify the functionally active genome of adult C57BL/6 mouse heart (AMH), we used serial analysis of gene expression (SAGE) to sequence a total of 88,860 tags or 23,941 unique tags. Over 66% of the unique tags matched either known genes or ESTs. Mitochondrial transcripts accounted for 18.7% of the total transcripts, whereas sarcomeric proteins accounted for 3.2% of all tags. After comparison of AMH expression profiles obtained by SAGE and cDNA arrays, we observed numerous quantitative discrepancies (for example: arrays, mt-Co1 > mt-Co2 > mt-Co3; SAGE, mt-Co1 >> mt-Co3 >or= mt-Co2). We carried out quantitative PCR analyses as an independent test of transcript abundance and determined that SAGE yielded quantitatively reliable data. These SAGE results thus represent the first quantitative expression profile of AMH and serve as a reliable transcriptome reference to identify dynamic changes in cardiac gene expression.

Animals↗

Differential expression of neuronal function genes follows a tissue-specific temporal dynamic during Deformed Wing Virus infection in honey bees.

Deformed Wing Virus type A (DWV-A) is one of the primary threats to honeybees (Apis mellifera), significantly impacting their nervous system physiology and behavior. While its neurotropic nature is well-recognized, the temporal dynamics of the neuronal transcriptomic response following oral infection, the natural transmission route, remains poorly understood. In this study, we analyzed gene expression in the heads of worker bees orally inoculated with DWV-A over a 16-day time course (1, 4, 7, 10, 13, and 16 days post-inoculation). RNA-seq analysis at day 10 identified 147 differentially expressed genes associated with different biological processes that are critical to the organism, including cellular metabolism and neuronal activity. RT-qPCR validation revealed a persistent downregulation of key genes related to glutamatergic system (eaat-2, neto, and kainate) and sensory perception-related genes in the antennae. Notably, the simultaneous co-expression of nurse-associated and forager-associated marker genes suggests that DWV-A infection induces an asynchrony in behavioral maturation. Our findings demonstrate that DWV-A disrupts neuronal homeostasis and peripheral sensory perception in a tissue-specific and time-dependent manner, providing a molecular framework to understand the behavioral impairment and the loss of coordination at the colony level.

Animals↗

Transcriptomic Association Between Poliovirus Receptor (PVR/CD155) and Claudin Signaling Pathways in Colorectal Cancer.

BACKGROUND/AIM: Enterotoxigenic Bacteroides fragilis promotes colorectal carcinogenesis through toxin-mediated cleavage of E-cadherin, a process facilitated by membrane-associated Claudin-4 (CLDN4). Separately, the poliovirus receptor (PVR/CD155) modulates tumor epithelial and immune dynamics. This study explored potential transcriptomic interactions and co-expression frameworks between PVR and claudin signaling pathways in colorectal cancer. MATERIALS AND METHODS: Transcriptomic and proteomic data from the The Cancer Genome Atlas-colon adenocarcinoma cohort (TCGA-COAD) were evaluated. An exploratory E-cadherin Cleavage Index was modeled to capture transcript-protein discordance. To control for tissue composition heterogeneity without mathematical circularity, a de-circularized, non-parametric partial rank residual model adjusted for independent CLDN4 expression was deployed within the stable microsatellite-stable (MSS) sub-cohort (N=473). RESULTS: Multivariable survival models showed no independent associations between overall survival and continuous PVR (p=0.79) or CLDN3 (p=0.56) expression. Robust linear modeling revealed no significant baseline interaction between PVR and CLDN4 regarding the exploratory Cleavage Index (p=0.82). However, de-circularized partial correlation analysis revealed a highly stable, positive co-expression between PVR and CLDN3 (rho=0.2459, p=3.23&#xd7;10-7). Both epithelial markers retained modest inverse correlations with the infiltrating lymphocytic axis (TIGIT and CD96). CONCLUSION: Baseline PVR expression is coordinated with CLDN3 tissue programs independent of general epithelial cellularity but does not interact with the CLDN4 axis or impact overall survival in an unexposed cohort. Because TCGA lacks virome or active microbial exposure tracking, these findings serve as baseline benchmarks for future context-dependent mechanistic studies.

Bacteroides fragilis toxin↗

Ovulatory surges of human CG prevent hormone-induced granulosa cell tumor formation leading to the identification of tumor-associated changes in the transcriptome.

Granulosa cell tumors comprise approximately 10% of ovarian tumors and, although rare, are clinically important due to their potential for malignancy and recurrence. Although their morphological features have been carefully described, the global changes in gene expression associated with their formation remain undetermined. To initiate this characterization, we used a transgenic mouse model in which granulosa cell tumors occur with 100% penetrance in CF-1 mice that harbor a novel transgene encoding a chimeric LHbeta subunit. When this transgene is expressed in other strains of mice, including (C57BL/6 female symbol x CF-1 male symbol,Tg) F1 hybrids, luteomas develop even though levels of LH remain high. This dichotomous response permits a longitudinal comparison of global changes in transcriptomes uniquely associated with either granulosa cell tumors or luteomas. Herein we report numerous changes in the transcriptome, including a decrease in LH receptor mRNA and increases in several mRNAs that encode secreted proteins previously associated with granulosa cell tumors. Furthermore, we identified a constellation of mRNAs that encode proteins that may serve as new markers for this tumor phenotype. Additional experiments indicated that periodic treatment with human CG prevented formation of granulosa cell tumors in mice genetically predisposed to tumor development and, instead, led to the appearance of luteomas. More importantly, ovarian transcriptomes from the luteomas induced by ovulatory doses of human CG permitted refined confirmation of gene expression changes that were uniquely associated with either granulosa cell tumors in the permissive CF-1 genetic background or in luteomas in the F1 hybrids. Together, these dynamic changes in the ovarian transcriptome indict various signaling pathways potentially involved in mediating the actions of LH over time and, depending on genetic background, the formation of either a luteoma or a granulosa cell tumor.

Animals↗

Transcriptome-wide analysis reveals sequence selection to avoid mRNA aggregation in E. coli.

The stability of RNA base pairing and its limited four-letter code create an intrinsic potential for promiscuous RNA-RNA interactions. In vitro, such interactions drive RNA to self-assemble into aggregates. This raises a fundamental unanswered question: within a confined cellular volume at physiological mRNA abundances, how much aggregation would arise from sequence-encoded chemistry alone? Here, we establish this baseline with large-scale kinetic simulations of the E. coli transcriptome. Our simulations reveal that sequence-encoded base-pairing energetics is sufficient to generate a dynamic network of large aggregates, organized by long, multivalent mRNA hubs. Strikingly, evolutionary analysis shows that native E. coli sequences exhibit clear signatures of selection to counteract this propensity: they fold more stably, minimize unstructured regions, and form weaker intermolecular contacts than dinucleotide-preserving controls. These findings demonstrate that maintaining transcriptome solubility has been a significant, previously unrecognized constraint shaping genome evolution, and provide a new lens to interpret cellular RNA management.

Biological Sciences (Biophysics and Computational ↗

Stage-specific remodeling of wingless-related integration sites (WNT) signaling during oocyte-to-embryo transition in pigs.

The WNT signaling pathway is a central regulator of cell polarity, adhesion, cytoskeletal dynamics, and lineage specification during early embryonic development. Although its roles have been extensively studied in murine and human models, the temporal regulation and pathway architecture of WNT signaling during early porcine development remain poorly defined. Here, we performed a comprehensive transcriptomic analysis to characterize WNT pathway dynamics across key stages of pig in vitro development, including immature oocytes (IMO), mature oocytes (MO), zygotes (ZY), cleaved embryos (2-4 cells; CL), and blastocysts (BL). Global analyses revealed major transcriptomic transitions (FDR <0.05; |Fold Change| &#x2265;2) during oocyte maturation and blastocyst formation, whereas zygotes and cleaved embryos exhibited highly similar expression profiles. Module-based and gene-level analyses showed that oocyte maturation is associated with increased expression of extracellular WNT antagonists and components of the &#x3b2;-catenin destruction complex, together with selective regulation of Frizzled receptors, consistent with tight control of canonical WNT signaling at the MII stage. Following fertilization, this inhibitory configuration was partially relieved, alongside transient upregulation of specific WNT ligands, transcriptional mediators, and adhesion-related components during zygotic genome activation and early cleavage. At the blastocyst stage, WNT signaling became increasingly associated with planar cell polarity and epithelial organization modules. Together, the data reveal a highly dynamic and stage-specific restructuring of WNT signaling during early porcine development. Our findings indicate that precise temporal modulation-rather than uniform activation-of WNT pathway components accompanies the porcine oocyte-to-embryo transition, providing a molecular framework to better understand early developmental regulation and offering insights relevant to reproductive biotechnology and developmental biology.

Wnt Signaling Pathway↗

Dynamic architecture of the yeast cell cycle uncovered by wavelet decomposition of expression microarray data.

Wavelet analysis has been applied to yeast cell cycle expression microchip data to reveal large-scale temporal structures and ubiquitous oscillations in mRNA levels. Discrete intervals in time within the cell cycle when expression levels changed were visualized as contour maps in which points of transition in gene expression among all 6178 genes were plotted as a function of cell cycle time. Time-frequency analysis using wavelet transforms supported the direct visualization and led to the conclusion that the predominant period is not the cell cycle but a higher frequency, 40 min, submultiple of the cycle. Each of the 6178 gene expression profiles was dissected by wavelet decomposition into all permitted frequencies from the Nyquist limit to roughly twice the cell cycle length. Transitions associated with maximum up- or down-regulation of mRNA levels appear as bands at circa 40-min intervals, half the length of the cycle, through two cell cycles. More than two thirds of the genes, including many of the cyclins, showed this half-cycle periodicity. Gene expression and events within the yeast cell cycle may be regulated by an attractor whose fundamental period is an emergent property of dynamic interactions within the yeast transcriptome.

Cell Cycle↗

Global analysis of gene expression using GeneChip microarrays.

DNA microarray technology, especially the use of GeneChip microarrays, has become a standard tool for parallel gene expression analysis. Recent improvements in GeneChip microarrays enable whole-genome expression analysis, and thus open a new avenue for studies of the composition, dynamics, and regulation of the transcriptome in plants.

Computational Biology↗

Sympatric European white oaks species display contrasting epigenetic response to soil water availability.

In the context of climate change plants have to cope with adverse conditions, among which water scarcity is a major threat for their survival. They have developed diverse regulatory processes to face drought that may differ depending on their ecological niche. The two sympatric oaks species (Quercus robur L. and Quercus petraea (Matt.). Liebl) have different levels of drought tolerance. We have investigated their strategies to face drought stress by analysing the transcriptome, small RNAome and methylome dynamics of young plants grown under control and drought stress conditions. Data indicate that cell wall remodeling is most likely involved in the better tolerance Q. petraea than of Q. robur. Furthermore, major methylation differences were identified between both oak species that were in part associated to their difference in drought stress responses. Integration of the three datasets revealed genomic co-locations of potential importance for forest tree adaptation to drought stress. Our data are consistent with species-specific molecular responses of oak to drought stress related to their ecological niches.

Forest trees- Omics- ecological niche↗

DNA chip technology in cardiovascular research.

Global and/or dynamic analysis of the cardiac transcriptome may improve our understanding of the adaptation of cardiac tissue or cells to different physiological or pathological conditions. The achievement of sequencing projects on mammalian genomes and the development of DNA chip technology have dramatically extended the scale of gene expression studies from a candidate gene approach to a system approach. In current DNA chip experiments, expression levels of thousands of genes can be determined simultaneously. Obviously, the huge quantities of objects and information generated by these experiments require a computational management of the expression data with adequate mathematical (mostly statistical) algorithms. Here, we will discuss the principle and experimental key points of DNA chips. Four examples will be cited to illustrate applications in the cardiovascular system.

Animals↗

Identification of cryosensitive niches and a targetable FOS/AP&#x2011;1 program in the human ovarian cortex by single&#x2011;cell and spatial transcriptomics.

BACKGROUND: The ovary is a vital and dynamic reproductive organ. Ovarian tissue cryopreservation (OTC) plays a vital role in preserving female fertility. However, the cellular subtypes most susceptible to cryoinjury and the molecular mechanisms underlying cryopreservation-associated damage remain poorly understood. This study aimed to identify cell populations vulnerable to freezing-thawing and to elucidate the key transcriptomic alterations and signaling pathways associated with ovarian cryoinjury at the single-cell and spatial levels. METHODS: Ovarian cortical tissues from patients undergoing three gender reassignment surgery (GRS) were divided into fresh and vitrification-rapid warming groups. Following collagenase IV digestion, 10x&#x2009;Genomics single-cell RNA-seq was used for dissociated ovarian cell suspensions (27,185 fresh and 25,480 frozen-thawed cells). Eight major cell clusters were identified. Additionally, 110 oocytes (66 fresh, 44 vitrification-rapid warming) were isolated and analyzed using the Smart-seq2 platform. Spatial transcriptomics was performed via BGI Stereo-seq. Molecular validation was performed via &#x3b2;-galactosidase staining, immunofluorescence, and qRT-PCR. RESULTS: Cryopreservation significantly altered the activity of pathways related to focal adhesion, oxidative stress, and apoptosis, particularly in stromal and perivascular cells. The number of FOS-positive perivascular cells was notably increased after vitrification-rapid warming, whereas the number of PTGDS-positive stromal cells decreased. Oocyte analysis revealed that cryopreservation primarily disrupted pathways involved in the cell cycle and meiosis, although the damage was not irreversible, supporting the relative safety of long-term cryostorage. Spatial transcriptomics and functional validation further confirmed the rapid and robust activation of the FOS/AP-1 pathway after vitrification-rapid warming, particularly in perivascular and granulosa cells. Treatment with T-5224 (a FOS/AP-1 inhibitor) significantly rescued the morphology and function of cultured frozen-thawed ovaries. CONCLUSIONS: Stromal and perivascular cells are the main cell types that are sensitive to ovarian cryopreservation. The FOS/AP-1 pathway is markedly activated after, suggesting the exacerbation of metabolic impairment. In oocytes within the ovarian cortex, the cell cycle and meiosis-related physiological processes were the primary processes affected.

Female↗