Biology subjects

Yun, Y.

Publications and source records attributed to Yun, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

A cohesion optimum underlies chromosome segregation fidelity in oocytes

Chromosome segregation is compromised in eggs from women of both early and advanced reproductive ages. Deteriorating cohesion causes premature separation of sister-chromatids in eggs from older females. We show that the converse is true for oocytes of adolescents, with excessive cohesion impeding segregation. Oocytes from juvenile mice show severe chromosome lagging in anaphase I, leading to nondisjunction or, in extreme cases, failure of the first meiotic division. These defects are suppressed by experimentally weakening cohesion or enhancing its resolution during anaphase I. By contrast, lagging and nondisjunction are rare in the oocytes of young adults because cohesion is inherently weaker. Thus, relative cohesion strength underlies both the frequency and type of segregation errors observed in eggs throughout the female reproductive lifespan. One-Sentence SummaryIn eggs, errors in chromosome segregation arise from age-dependent imbalances in how tightly chromosomes are held together.

cell biology↗

bioRxiv2026

SUMO mediates the coordinate regulation of meiotic chromosome length and crossover rate

Meiotic prophase-I chromosomes are organized into linear arrays of chromatin loops anchored to proteinaceous axes that define the interaction interfaces for the pairing and synapsis of homologous chromosomes. Chromatin loop size and axial chromosome length are inversely correlated and vary widely both between and within species, including between the sexes. The molecular basis of this variation remains unclear. Here, we provide evidence that the small ubiquitin-like modifier, SUMO, regulates loop-axis organization in mouse meiosis. Our analysis shows that the longer axes of oocyte chromosomes contain more SUMO per unit length than the shorter axes of spermatocyte chromosomes. In mouse models, the loss of SUMO1 results in shorter axes and longer chromatin loops. Conversely, increased SUMO1 conjugation, caused by mutation of the SENP1 isopeptidase, produces longer axes with shorter loops. Axis length positively correlates with meiotic recombination. Accordingly, Sumo1 and Senp1 mutations respectively decrease and increase crossover frequency. These findings identify SUMO as a key regulator of meiotic chromosome architecture and suggest a molecular basis for the physiological variation in chromosome length and recombination rates seen among species, sexes, individuals, and individual meiocytes. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/710713v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@145c465org.highwire.dtl.DTLVardef@160c8aborg.highwire.dtl.DTLVardef@1165b76org.highwire.dtl.DTLVardef@ced5e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

High-resolution single-cell RNA sequencing using canFam4 reveals novel immune subsets and checkpoint programs in healthy dogs

Single-cell RNA sequencing (scRNA-seq) enables high-resolution profiling of immune heterogeneity. Although previous studies have mapped the single-cell transcriptomic atlases of peripheral leukocytes in healthy dogs, the identification and functional characterization of distinct immune subsets remain incomplete. We constructed a single-cell atlas of peripheral leukocytes from six healthy small-breed dogs using the 10x Genomics platform and the updated canFam4 genome. Analysis of 30,040 high-quality transcriptomes revealed 51 distinct immune subsets, including CD14{square}CD33{square} monocytes, XCR1{square}CD1D{square} dendritic cells, CEACAM1{square}CD24{square} neutrophils, and IL32{square}BATF{square} regulatory T cells, which were underrepresented in canFam3.1-based studies. Interferon-enriched CD14{square} monocytes and CD4{square} T subsets associated with myxomatous mitral valve disease were also identified. Functional analysis revealed that PDCD1 attenuates TCR signaling, LAG3 modulates malate metabolism in CD4{square} T cells, and suppresses TBX21 in CD8{square} T cells associated with viral response. CD274 encoding PD-L1 was linked to IL-10 production in neutrophils, and CTLA4 represented an initial activation of double-negative T subsets. T cell exhaustion scores and proliferative fractions varied across cohorts, reflecting differences in environmental antigenic exposures. Our study represents the first comprehensive, gene-resolved single-cell analysis that reveals immunoregulatory checkpoint mechanisms underlying immune homeostasis in healthy dogs. Our dataset will serve as a valuable resource for future comparative and translational immunology research in dogs.

immunology↗

bioRxiv2025

An arginine switch drives the stepwise activation of β-arrestin

{beta}-arrestins ({beta}arrs) play a crucial role in regulating G protein-coupled receptor (GPCR) signaling and trafficking. Canonically, interactions of {beta}arr with the phosphorylated intracellular GPCR-tail induce a multi-step conformational transition that results in the activation of {beta}arr. Depending on the specific interaction pattern with the receptor, {beta}arrs adopt multiple conformational states, each tightly linked to a specific functional outcome of {beta}arr recruitment. Despite its physiological relevance, the structural determinants of {beta}arr activation remain poorly understood. Using a combination of molecular dynamics simulations, biochemical and cell-based experiments, we reveal how specific interactions with a prototypical GPCR promote the unbinding of the {beta}arr2 C-tail--a crucial step in arrestin activation. Importantly, we observe that the expulsion of the C-tail is promoted by the displacement of a conserved arginine residue (Arg394) within the {beta}arr polar core, which we dub "the arginine switch." Our study uncovers a previously unknown molecular switch that, upon engagement, destabilizes the polar core as a crucial step in the GPCR-induced {beta}arr activation.

biochemistry↗

bioRxiv2024

Characterizing interactions of ER resident proteins in situ through the YST-PPI method

The mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.

microbiology↗

bioRxiv2024

An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung

Severe lung injury causes basal stem cells to migrate and outcompete alveolar stem cells resulting in dysplastic repair and a loss of gas exchange function. This "stem cell collision" is part of a multistep process that is now revealed to generate an injury-induced tissue niche (iTCH) containing Keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Temporal and spatial single cell analysis reveals that iTCHs are governed by mesenchymal proliferation and Notch signaling, which suppresses Wnt and Fgf signaling in iTCHs. Conversely, loss of Notch in iTCHs rewires alveolar signaling patterns to promote euplastic regeneration and gas exchange. The signaling patterns of iTCHs can differentially phenotype fibrotic from degenerative human lung diseases, through apposing flows of FGF and WNT signaling. These data reveal the emergence of an injury and disease associated iTCH in the lung and the ability of using iTCH specific signaling patterns to discriminate human lung disease phenotypes.

cell biology↗

bioRxiv2023

Golgi-associated retrograde protein (GARP) complex recruits retromer to trans-Golgi network for FgKex2 and FgSnc1 recycling, necessary for development and pathogenicity of Fusarium graminearum

In eukaryotic cells, the retromer complex plays a crucial role in orchestrating the sorting and retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN). Despite its significance, the molecular details of this intracellular trafficking process remain unclear. Here, we identified a Golgi-associated retrograde protein (GARP) complex as a mediator of vesicular transport, facilitating the recruitment of the retromer complex to TGN to exert its functions. The GARP complex is mainly localized to the TGN, where it interacts with the retromer complex. This interaction is evolutionarily conserved across different species. Furthermore, we identified FgKex2 and Fgsnc1 as cargo proteins in the GARP/retromer-mediated recycling pathway. Loss of GARP or retromer results in a complete mis-sorting of FgKex2 and FgSnc1 to the vacuolar degradation pathway, which affects the growth, development, toxisome biogenesis, and pathogenicity of F. graminearum. In summary, we assert that GARP facilitates the recruitment of retromer from endosomes to the TGN, orchestrating the recycling of FgKex2 and FgSnc1. This is integral to sustaining continuous growth, development and contributes significantly to the pathogenicity of F. graminearum.

microbiology↗

bioRxiv2023

Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis

During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation at the first division, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, crossover patterning results from nascent recombination sites competing to accrue a limiting pro-crossover RING-domain protein (COR) that diffuses between synapsed chromosomes. Here we delineate the localization dynamics of three mammalian CORs in mouse and determine their interdependencies. RNF212, HEI10 and a new member RNF212B show divergent spatiotemporal dynamics along synapsed chromosomes, including profound differences in spermatocytes and oocytes, that are not easily reconciled by elementary coarsening models. Contrasting mutant phenotypes and genetic requirements indicate that RNF212B, RNF212, and HEI10 play distinct but interdependent functions in regulating meiotic recombination and coordinating the events of meiotic prophase-I by integrating signals from DNA breaks, homolog synapsis, the cell-cycle, and incipient crossover sites. SIGNIFICANCEMeiosis produces haploid gametes by precisely halving the chromosome complement. Crossing over between homologous chromosomes (homologs) is essential for their accurate segregation and defects are associated with infertility, miscarriage, and congenital disease. Factors that ensure crossing over between each pair of homologs include mammalian RING-domain proteins RNF212, HEI10, and RNF212B, alleles of which are linked to infertility and heritable variation in crossover rate. This study focuses on understanding the functions and relationships between pro-crossover RING proteins (CORs) in mouse, providing important insights into their roles in regulating recombination, the DNA repair process that gives rise to crossovers. Notably, chromosomal localization dynamics of the three CORs are distinct and show striking sexual dimorphism with important implications for models of crossover control.

genetics↗

bioRxiv2022

Reduced oocyte quality and exacerbation of the maternal age effect are enduring consequences of low-level atrazine exposure in mouse

BACKGROUNDEgg development has unique features that render it vulnerable to environmental perturbation. The herbicide atrazine is an endocrine disruptor shown to have detrimental effects on reproduction across a number of vertebrate species. OBJECTIVESTo determine whether exposure to low levels of atrazine impairs meiosis in female mammals using a mouse model; in particular, whether and how the fidelity of oocyte chromosome segregation is affected, and whether the aging-related aneuploidy is exacerbated. METHODSFemale C57BL/6J mice were exposed to two levels of atrazine in drinking water, with the lower level corresponding to detected environmental contamination. To model exposure during development, atrazine was ingested by pregnant females at 0.5 days post coitum and continued until pups were weaned at 21 days post-partum. For adult exposure, 2-month-old females ingested atrazine for 3 months. For each exposure group, various indicators of oocyte quality were determined, including developmental capacity and chromosomal abnormalities during the two meiotic divisions. RESULTSDevelopmental exposure caused only minor effects on the fetal events of meiotic prophase-I and establishment of initial follicle pools. However, ovulation was enhanced while oocyte quality was significantly reduced. At the chromosome level, misalignment and numerical and structural abnormalities were increased at both meiotic divisions. Furthermore, fertilization efficiency was impaired in vitro, and apoptosis was elevated in blastocysts derived from the eggs of atrazine-exposed females. Similar levels of chromosomal defects were seen in oocytes following both developmental and adult exposure regimens suggesting that quiescent primordial follicles may be the consequential targets of atrazine. Importantly, defects were observed long after exposure was terminated. Moreover, dramatic increases in chromosomally abnormal oocytes were seen in older mice indicating that atrazine exposure during development exacerbates the effects of maternal aging on oocyte quality. Indeed, analogous to the effects of maternal age, atrazine exposure resulted in weakened cohesion between sister chromatids. CONCLUSIONLow-level atrazine exposure causes persistent changes to the female mammalian germline with potential consequences for reproductive lifespan and congenital disease.

pharmacology and toxicology↗

bioRxiv2022

Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system

Chemokine receptors constitute an important subfamily of G protein-coupled receptors (GPCRs), and they are critically involved in a broad range of immune response mechanisms. Ligand promiscuity among these receptors makes them an interesting target to explore novel aspects of biased agonism. Here, we comprehensively characterize two chemokine receptors namely, CXCR4 and CXCR7, which share a common chemokine agonist (CXCL12), in terms of their G-protein coupling, {beta}-arrestin ({beta}arr) recruitment, contribution of GRKs, and ERK1/2 MAP kinase activation. We observe that CXCR7 lacks G-protein coupling while maintaining robust {beta}arr recruitment with a major contribution of GRK5/6. On the other hand, CXCR4 displays robust G-protein activation as expected, however, it exhibits significantly reduced {beta}arr-coupling compared to CXCR7 in response to their shared natural agonist, CXCL12. These two receptors induce distinct {beta}arr conformations even when activated by the same agonist, and CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase. We further determine the crystal structure of {beta}arr2 in complex with a carboxyl-terminal phosphopeptide derived from CXCR7, which reveals a smaller interdomain rotation than observed previously for activated {beta}arrs. Importantly, structure-guided cellular experiments reveal a key contribution of a single phosphorylation site in CXCR7 on {beta}arr recruitment and endosomal trafficking. Taken together, our study provides molecular insights into intrinsic bias encoded in the CXCR4-CXCR7 system, and it has broad implications for therapeutically important framework of biased agonism.

biochemistry↗

bioRxiv2022

ECPAS/Ecm29-Mediated 26S Proteasome Disassembly Is an Adaptive Response to Glucose Starvation

The 26S proteasome consists of loosely associated 20S catalytic and 19S regulatory complexes. Approximately half of the proteasomes in eukaryotic cells exist as free 20S complexes; however, our mechanistic and physiological understanding of what determines the ratio of 26S to 20S species remains incomplete. Here, we show that glucose starvation in mammalian cells results in the uncoupling of 26S holoenzymes into intact 20S and 19S subcomplexes. Subcomplex affinity-purification and quantitative mass spectrometry revealed that Ecm29 proteasome adaptor and scaffold (ECPAS) is a crucial mediator of this structural remodeling. The loss of ECPAS abrogated 26S dissociation, leading to decreased degradation of 20S proteasome substrates such as puromycylated polypeptides and lysine-less cyclin B. In silico modeling analysis suggested that the conformational changes of ECPAS may commence the disassembly process. ECPAS was also essential for proper endoplasmic reticulum stress response and cell survival during glucose starvation. In addition, we evaluated the role of ECPAS in vivo using the mouse xenograft model and observed that glucose-deprived tumor tissues had significantly elevated 20S proteasome levels. Collectively, our results indicate that the 20S-19S disassembly mediated by ECPAS is a novel mechanism adapting global proteolysis to physiological needs and an effective cellular strategy against proteotoxic stress.

biochemistry↗

bioRxiv2022

Molecular mechanisms of microbiome modulation by the diatom secondary metabolite azelaic acid

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a C4-TRAP transporter, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8x10-9 nmol cell-1 hr-1 and utilized it as a carbon source in concentrations ranging from 10 M-1 mM, suggesting a broad range of acclimation to Aze availability. For inhibited bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolise Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

ecology↗

bioRxiv2021

A novel high-throughput assay using mixed genomic DNA for fast screening germline pathogenic variants in breast cancer susceptibility genes

The demand for genetic testing for breast cancer susceptibility genes is increasing for both breast cancer patients and healthy individuals. Here we established a novel high-throughput assay to detect germline pathogenic variants in breast cancer susceptibility genes. In general, up 10 to 50 individual genomic DNA samples were mixed together to create a mixed DNA sample and the mixed DNA sample was subjected to a next-generation multigene panel. Germline pathogenic variants in breast cancer susceptibility genes could be found in the mixed DNA sample; next, site-specific Sanger sequencing was performed to identify individuals who carried he pathogenic variant in the mixed samples. We found that the recall and precision rates were 89.9% and 92.9% when twenty individual genomic samples were mixed. Therefore, our new assay can increase an approximately 20-fold of efficacy to identify the pathogenic variants in breast cancer susceptibility genes in individuals when compared with current assay.

genetics↗

bioRxiv2021

Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor

Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

biophysics↗

bioRxiv2020

Development of Targetable Multi-Drug Nanoparticles for Glioblastoma Treatment and In Vitro Evaluation in Glioblastoma Stem Cells

Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis. The current median survival is approximately fifteen to twenty months with the standard of care therapy which includes surgery, radiation, and chemotherapy. An important factor contributing to recurrence of GBM is high resistance of GBM cancer stem cells (CSCs) to several anticancer drugs, for which a systemically delivered single drug approach will be unlikely to produce a viable cure. Therefore, multidrug therapies have the potential to improve the survival time. Currently, only temozolomide (TMZ), which is a DNA alkylator, affects overall survival in GBM patients. CSCs regenerate rapidly and over-express a methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to drug resistance. Idasanutlin (RG7388, R05503781) is a potent, selective MDM2 antagonist that additively kills GBM CSCs when combined with TMZ. Nanotechnology is an emerging field that shows great promise in drug delivery and diagnostics. The ability to combine both therapy and imaging allows real time assessment of drug delivery in vivo for the field of theranostics. To develop a multi-drug therapy using multi-functional nanoparticles (NPs) that preferentially target the GBM CSC subpopulation and provide in vivo preclinical imaging capability. Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed investigating both single and double emulsion fabrication techniques as well as combinations of TMZ and RG7388. The NPs were covalently bound to a 15-base-pair CD133 aptamer in order to target the CD133 antigen expressed on the surface of GBM CSC subpopulation. For theranostic functionality, the NPs were also labelled with a radiotracer, Zirconium-89 (89Zr). The NPs maintained a small size of less than 100 nm, a low negative charge and exhibited the ability to effectively target and kill the CSC subpopulation. In addition, the conjugation of the CD133 aptamer was able to promote killing in CSCs leading to the justification of a targeted nanosystem to potentially improve localized therapy in future in vivo models. This work has provided a potentially therapeutic option for GBM specific for CSC targeting and theranostic imaging.

cell biology↗

bioRxiv2020

Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma

Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking have rendered glioblastoma (GBM) highly resistant to therapy. As a result, GBM immunotherapies have failed to demonstrate sustained clinical improvements in patient overall survival (OS). To overcome these obstacles, here we describe a novel, sophisticated combinatorial platform for GBM: the first multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses key drivers of GBM resistance to therapy: antigen escape, poor immune cell homing, and immunometabolic reprogramming of immune responses. We engineered dual-specific CAR-NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally-released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site specific activity in the tissue and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells, but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising new NK cell-based combinatorial strategy that can target multiple clinically-recognized mechanisms of GBM progression simultaneously.

immunology↗

bioRxiv2020

Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs

Uncovering conserved 3D protein-ligand binding patterns at the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design.

bioinformatics↗

bioRxiv2018

Maternal Obesity Enhances Oocyte Chromosome Abnormalities Associated With Aging

Obesity is increasing globally and maternal obesity has adverse effects on pregnancy outcomes and the long-term health of offspring. Maternal obesity has been associated with pregnancy failure through impaired oogenesis and embryogenesis. However, whether maternal obesity causes chromosome abnormalities in oocytes has remained unclear. Here we show that chromosome abnormalities are increased in the oocytes of obese mice and identify weakened sister-chromatid cohesion as the likely cause. Numbers of full-grown follicles retrieved from obese mice were the same as controls and the efficiency of in vitro oocyte maturation remained high. However, chromosome abnormalities presenting in both metaphase-I and metaphase-II were elevated, most prominently the premature separation of sister chromatids. Weakened sister-chromatid cohesion in oocytes from obese mice was manifested both as the terminalization of chiasmata in metaphase-I and as increased separation of sister centromeres in metaphase II. Obesity-associated abnormalities were elevated in older mice implying that maternal obesity exacerbates the deterioration of cohesion seen with advancing age.

genetics↗