bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–05–11
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. AURKA controls oocyte spindle assembly checkpoint and chromosome alignment by HEC1 phosphorylation.
  2. ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development.
  3. Rab32-based vesicles coordinate mitochondria and actin for spindle migration and organelle rearrangement in oocyte meiosis.
  4. Human-specific contributors to cleavage-stage embryonic arrest during maternal to zygotic transition.
  5. 3D-organization and spatial localization of chromatin and epigenetic marks linked to nucleolar activity in porcine oocytes.
  6. Single-cell metabolomics reveals that bisphosphoglycerate mutase influences oocyte maturation through glucose metabolism.
  7. Common variation in meiosis genes shapes human recombination phenotypes and aneuploidy risk.
  8. Slow awakening of the silent X chromosome in female primordial germ cells.
  9. Protocol for induction, maintenance, and exit from embryo dormancy in mice.
  10. Conservation and divergence of the molecular regulators of the vertebrate fertilization synapse.
  11. Mapping the anatomical and transcriptional landscape of early human fetal ovary development.
  1. Life Sci Alliance. 2025 Jul;pii: e202403146. [Epub ahead of print]8(7):
    AURKA controls oocyte spindle assembly checkpoint and chromosome alignment by HEC1 phosphorylation.
    Cecilia S Blengini, Shuang Tang, Robert J Mendola, G John Garrisi, Jason E Swain, Karen Schindler.
      In human oocytes, meiosis I is error-prone, causing early miscarriages and developmental disorders. The Aurora protein kinases are key regulators of chromosome segregation in mitosis and meiosis, and their dysfunction is associated with aneuploidy. Oocytes express three Aurora kinase (AURK) proteins, but only AURKA is necessary and sufficient to support oocyte meiosis in mice. However, the unique molecular contributions to ensuring high egg quality of AURKA remain unclear. Here, using a combination of genetic and pharmacological approaches, we evaluated how AURKA phosphorylation regulates outer kinetochore function during oocyte meiosis. We found that the outer kinetochore protein Ndc80/HEC1 is constitutively phosphorylated at multiple residues by Aurora kinases during meiosis I, but that serine 69 is specifically phosphorylated by AURKA in mouse and human oocytes. We further show that serine 69 phosphorylation contributes to spindle assembly checkpoint activation and chromosome alignment during meiosis I. These results provide a fundamental mechanistic understanding of how AURKA regulates meiosis and kinetochore function to ensure meiosis I fidelity.
    DOI:  https://doi.org/10.26508/lsa.202403146
  2. Genome Biol. 2025 May 08. 26(1): 120
    ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development.
    Yu-Ke Wu, Ruibao Su, Zhi-Yan Jiang, Yun-Wen Wu, Yan Rong, Shu-Yan Ji, Jingwen Liu, Zhuoyue Niu, Zhiyi Li, Yuanchao Xue, Falong Lu, Heng-Yu Fan.
       BACKGROUND: During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability.
    RESULTS: Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3'-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs.
    CONCLUSIONS: The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.
    Keywords:  Maternal-to-zygotic transition; Meiosis; Oocyte transcriptome; RNA polyadenylation; RNA-binding proteins
    DOI:  https://doi.org/10.1186/s13059-025-03593-8
  3. J Adv Res. 2025 May 03. pii: S2090-1232(25)00294-2. [Epub ahead of print]
    Rab32-based vesicles coordinate mitochondria and actin for spindle migration and organelle rearrangement in oocyte meiosis.
    Hao-Lin Zhang, Qian Cui, Xiao-Ting Yu, Yu-Xuan Hou, Rui-Jie Ma, Ping-Shuang Lu, Yue Wang, Shao-Chen Sun, Hong-Hui Wang.
       INTRODUCTION: Rab32 is a part of the Rab GTPase family, which is known as the regulator of vesicle transport for an array of cellular functions including endosomal transport, autophagy, generation of melanosomes, phagocytosis and inflammatory processes.
    OBJECTIVE: However, the role of Rab32 in oocyte meiosis is still not well-defined.
    METHODS: We depleted Rab32 expression by knock down approach, and we also disrupted Rab32 function by exogenous Rab32Q83L/T37N mRNA injection for mutation.
    RESULTS: In our current investigation, we delved into its impacts on the cytoskeleton dynamics and the functionality of organelles during the meiotic maturation process in mouse oocytes. Rab32 expressed during oocyte meiosis and deletion of Rab32 or the expression of exogenous Rab32Q83L/T37N led to oocyte polar body extrusion defects or symmetric division. We showed that Rab32 was essential for ROCK1-based actin assembly which further led to spindle migration for the asymmetry. Besides, perturbation of Rab32 affected DRP1 phosphorylation for the spatial arrangement and functionality of mitochondria in mouse oocytes. And we found that Rab32 disruption caused the miscarriage of membrane organelles such as Golgi apparatus, ER, lysosome and CGs during oocyte meiosis, leading to ER stress and autophagy.
    CONCLUSIONS: In summary, our study unravels the critical functions of Rab32 for the interplay between actin and mitochondria, which further facilitates movement of the spindle apparatus and organelles arrangement in mouse oocyte meiotic development.
    Keywords:  Actin; Meiosis; Mitochondria; Organelles; Rab32
    DOI:  https://doi.org/10.1016/j.jare.2025.05.001
  4. Dev Cell. 2025 May 05. pii: S1534-5807(25)00209-6. [Epub ahead of print]60(9): 1277-1279
    Human-specific contributors to cleavage-stage embryonic arrest during maternal to zygotic transition.
    Mehmet-Yunus Comar, Bernardo Oldak, Jacob H Hanna.
      Understanding the functional regulatory landscape of maternal-to-zygotic transition (MZT) during early human embryo development remains a challenge. In this issue of Developmental Cell, Guo et al. assessed single-cell allele-specific transcriptomics from human preimplantation embryos and identified DPRX and ARGFX genes as pivotal factors whose hampered activation underlies cleavage-stage embryonic arrest.
    DOI:  https://doi.org/10.1016/j.devcel.2025.04.007
  5. Biol Reprod. 2025 May 03. pii: ioaf098. [Epub ahead of print]
    3D-organization and spatial localization of chromatin and epigenetic marks linked to nucleolar activity in porcine oocytes.
    Merle Fenner, Michal Benc, Alexandra Rosenbaum Bartkova, Maria Pihl, Martine Chebrout, Martine Letheule, Frantisek Strejcek, Poul Hyttel, Jozef Laurincik, Kristine Freude, Amelié Bonnet-Garnier.
      Previous murine studies have established that large-scale chromatin modifications upon completion of oocyte growth are associated with nucleolar transcriptional silencing. These modifications seem essential both for completion of the oocyte's meiosis and subsequent embryonic developmental success. Investigating this putative interconnection between nucleolar transcriptional activity and spatial chromatin organization towards completion of oocyte growth in pigs, we scrutinized whether 3D chromatin organization and heterochromatin localization, along with epigenetic markers, could indicate oocyte quality and predict developmental competence of harvested porcine oocytes. Supravital brilliant-cresyl-blue (BCB) staining was used to classify porcine cumulus-oocyte-complexes (COCs) as fully grown (BCB+) or still growing (BCB-). Oocytes were analyzed via integrated 3D-immunofluorescence for nucleolar activity and heterochromatin markers, as well as 3D-DNA-FISH for specific heterochromatin sequences. Additionally, some oocytes were prepared for transmission electron microscopy (TEM). TEM revealed distinct ultrastructural differences between BCB+ and BCB- oocytes and validated BCB-staining as viable method for a rough assessment of oocyte developmental competence. Immunostaining identified all known germinal vesicle (GV) chromatin configurations (non-surrounded nucleolus (NSN), partially non-surrounded nucleolus (pNSN), partially surrounded nucleolus (pSN), surrounded nucleolus (SN)) and linked them to respective BCB categories. Nucleolar activity was detected only in NSN oocytes, predominantly from the BCB- group. Protein markers and FISH signals revealed significant 3D-organizational changes in chromatin between NSN and SN conformations, clustering around the nucleolus towards final oocyte maturation. These findings highlight an evident interconnection between nucleolar transcriptional silencing and specific 3D chromatin organization patterns, with changes in heterochromatin localization indicating completion of the oocytes' growth phase and marking higher competency for subsequent final maturation and embryonic development.
    Keywords:  Brilliant cresyl blue; Chromatin conformation; Epigenetics; Nucleolar sphere; Oocyte developmental biology; Pericentromeric satellite dna; Porcine oocytes; Transcriptional activity
    DOI:  https://doi.org/10.1093/biolre/ioaf098
  6. Mol Hum Reprod. 2025 May 05. pii: gaaf009. [Epub ahead of print]
    Single-cell metabolomics reveals that bisphosphoglycerate mutase influences oocyte maturation through glucose metabolism.
    Jing Wang, Qiang Liu, Zhiqiang Yan, Qianying Guo, Yixuan Wu, Ling Ding, Tianyi Liao, Jiahui Fan, Jie Qiao, Liying Yan.
      The spatiotemporal turnover of metabolites is essential for oocyte maturation, embryonic development, and cell lineage differentiation. Here, we analyzed the metabolic profiles of individual living mouse oocytes and studied how bisphosphoglycerate mutase (BPGM), an important maternal factor, influences metabolite regulation during oocyte maturation. We find that BPGM is expressed in mouse follicles, oocytes, and embryos, as well as in human embryos. Notably, deletion of Bpgm significantly reduced the rate of oocyte maturation and reduced mouse fertility, observed as reduced pups per litter. Also, the expression levels for meiosis-related genes and genes related to glucose metabolic pathways (glycolysis, tricarboxylic acid cycle, and pentose phosphate pathway) were altered in BPGM-deficient mouse oocytes. We used a highly sensitive, live-cell sampling approach to carry out metabolite assays using induced nano-electrospray-ionization mass spectrometry (InESI/MS) technology on 1 picolitre (pL) of aspirated cytoplasm from oocytes. BPGM gene disruption impaired glucose metabolism pathways, tyrosine metabolism and amino acid biosynthesis. Together, our findings indicate that Bpgm participates in oocyte and embryo development, and we demonstrate the feasibility of studying metabolite composition and other phenotypic features of single oocytes.
    Keywords:  BPGM; embryo; oocyte; single-cell RNA-seq; single-cell metabolomics
    DOI:  https://doi.org/10.1093/molehr/gaaf009
  7. medRxiv. 2025 Apr 04. pii: 2025.04.02.25325097. [Epub ahead of print]
    Common variation in meiosis genes shapes human recombination phenotypes and aneuploidy risk.
    Sara A Carioscia, Arjun Biddanda, Margaret R Starostik, Xiaona Tang, Eva R Hoffmann, Zachary P Demko, Rajiv C McCoy.
      The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis. While abnormal crossover recombination is known to confer risk for aneuploidy, limited data have hindered understanding of the potential shared genetic basis of these key molecular phenotypes. To address this gap, we performed retrospective analysis of preimplantation genetic testing data from 139,416 in vitro fertilized embryos from 22,850 sets of biological parents. By tracing transmission of haplotypes, we identified 3,656,198 crossovers, as well as 92,485 aneuploid chromosomes. Counts of crossovers were lower in aneuploid versus euploid embryos, consistent with their role in chromosome pairing and segregation. Our analyses further revealed that a common haplotype spanning the meiotic cohesin SMC1B is significantly associated with both crossover count and maternal meiotic aneuploidy, with evidence supporting a non-coding cis -regulatory mechanism. Transcriptome- and phenome-wide association tests also implicated variation in the synaptonemal complex component C14orf39 and crossover-regulating ubiquitin ligases CCNB1IP1 and RNF212 in meiotic aneuploidy risk. More broadly, recombination and aneuploidy possess a partially shared genetic basis that also overlaps with reproductive aging traits. Our findings highlight the dual role of recombination in generating genetic diversity, while ensuring meiotic fidelity.
    DOI:  https://doi.org/10.1101/2025.04.02.25325097
  8. Nat Struct Mol Biol. 2025 May 05.
    Slow awakening of the silent X chromosome in female primordial germ cells.
    Christine M Disteche, Xinxian Deng.
      
    DOI:  https://doi.org/10.1038/s41594-025-01550-4
  9. STAR Protoc. 2025 May 06. pii: S2666-1667(25)00219-9. [Epub ahead of print]6(2): 103813
    Protocol for induction, maintenance, and exit from embryo dormancy in mice.
    Rui Chen, Rui Fan, Ivan Bedzhov.
      Embryonic dormancy (diapause) is a reproductive adaptation that allows some mammalian species to prolong pregnancy and delay birth by temporarily suspending embryonic development just before implantation. Here, we present a step-by-step protocol for inducing and maintaining embryonic diapause in mice by tamoxifen administration or ovariectomy. We describe steps for setting up mouse matings, the administration of pharmacological compounds, the surgical procedure for the removal of the ovaries, postoperative care, and the isolation of dormant embryos. We then describe procedures for triggering exit from diapause by administration of β-estradiol and the subsequent isolation of reactivated embryos. For complete details on the use and execution of this protocol, please refer to Chen et al.1.
    Keywords:  Cell Biology; Developmental biology; Genetics; Metabolism; Model Organisms; Stem Cells
    DOI:  https://doi.org/10.1016/j.xpro.2025.103813
  10. Curr Opin Genet Dev. 2025 May 07. pii: S0959-437X(25)00044-9. [Epub ahead of print]93 102352
    Conservation and divergence of the molecular regulators of the vertebrate fertilization synapse.
    Andreas Blaha, Alexander Schleiffer, Andrea Pauli.
      Fertilization - the process during which sperm and egg find each other, bind and eventually fuse - marks the beginning of a new individual. Research over the past years in vertebrates has shed new light on conserved and divergent molecular regulators that mediate the formation of the fertilization synapse, the close apposition of the two plasma membranes before fusion. Here, we review the known proteins that are required for sperm-egg interaction in mammals and fish from a phylogenetic perspective. While some sperm factors are only conserved in vertebrates and share phylogenetic and structural features, others have a longer evolutionary history. In contrast, the egg factors have changed even within vertebrates despite recognizing the preserved sperm machinery. Future functional work on these factors will be essential to understand the fusion mechanism of vertebrate sperm and egg.
    DOI:  https://doi.org/10.1016/j.gde.2025.102352
  11. Sci Rep. 2025 May 06. 15(1): 15814
    Mapping the anatomical and transcriptional landscape of early human fetal ovary development.
    Sinead M McGlacken-Byrne, Ignacio Del Valle, Theodoros Xenakis, Ian C Simcock, Jenifer P Suntharalingham, Federica Buonocore, Berta Crespo, Nadjeda Moreno, Danielle Liptrot, Paola Niola, Tony Brooks, Gerard S Conway, Mehul T Dattani, Owen J Arthurs, Nita Solanky, John C Achermann.
      The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary (or Premature) Ovarian Insufficiency and Differences of Sex Development. We combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus computed tomography to elucidate the anatomy and transcriptional landscape of the human fetal ovary across key developmental timepoints (Carnegie Stage 22 until 20 weeks post conception). We show the marked growth and distinct morphological changes within the fetal ovary at the critical timepoint of germ cell expansion and demonstrate that the fetal ovary becomes more transcriptomically distinct from the testis with age. We describe previously uncharacterised ovary developmental pathways, relating to neuroendocrine signalling, energy homeostasis, mitochondrial networks, and inflammasome regulation. We define transcriptional regulators and candidate genes for meiosis within the developing ovary. Together, this work advances our fundamental understanding of human ovary development and has relevance for human ovarian insufficiency phenotypes.
    Keywords:  Micro-focus computed tomography; Ovarian insufficiency; Ovary development; Ovary function; Transcriptomics
    DOI:  https://doi.org/10.1038/s41598-025-96135-y
This page is being maintained by Thomas Krichel. It was last updated on 2025‒05‒11 at 7:39.