bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2024–12–22
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Isolation and manipulation of meiotic spindles from mouse oocytes reveals migration regulated by pulling force during asymmetric division.
  2. PGC7 regulates maternal mRNA translation via AKT1-YBX1 interactions in mouse oocytes.
  3. Identification of the Polo-like kinase substrate required for homologous synapsis.
  4. Genetic Abnormalities of Oocyte Maturation: Mechanisms and Clinical Implications.
  5. Low-input CUT&Tag for efficient epigenomic profiling of zebrafish stage I oocytes.
  6. Age-associated accumulation of RAB9 disrupts oocyte meiosis.
  7. The GPER is an important factor through which somatic cells regulate oocyte maternal mRNA translation and developmental competence.
  8. Germ cell development: Anchoring and pulling forces shape germline cyst construction.
  9. Identifying the composition of large vesicles in the cytoplasm of oocytes.
  10. Transcriptomic analysis and epigenetic regulators in human oocytes at different stages of oocyte meiotic maturation.
  11. The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review.
  1. bioRxiv. 2024 Dec 08. pii: 2024.12.06.627260. [Epub ahead of print]
    Isolation and manipulation of meiotic spindles from mouse oocytes reveals migration regulated by pulling force during asymmetric division.
    Ning Liu, Ryo Kawamura, Wenan Qiang, Ahmed Balboula, John F Marko, Huanyu Qiao.
      Spindles are essential for accurate chromosome segregation in all eukaryotic cells. This study presents a novel approach for isolating fresh mammalian spindles from mouse oocytes, establishing it as a valuable in vitro model system for a wide range of possible studies. Our method enables the investigation of the physical properties and migration force of meiotic spindles in oocytes. We found that the spindle length decreases upon isolation from the oocyte. Combining this observation with direct measurements of spindle mechanics, we examined the forces governing spindle migration during oocyte asymmetric division. Our findings suggest that the spindle migration is regulated by a pulling force and a net tensile force of approximately 680 pN is applied to the spindle in vivo during the migration process. This method, unveiling insights into spindle dynamics, holds promise as a robust model for future investigations into spindle formation and chromosome separation. We also found that the same approach could not isolate spindles from somatic cells, indicative of mammalian oocytes having a unique spindle organization amenable to isolation.
    DOI:  https://doi.org/10.1101/2024.12.06.627260
  2. Cell Commun Signal. 2024 Dec 18. 22(1): 604
    PGC7 regulates maternal mRNA translation via AKT1-YBX1 interactions in mouse oocytes.
    Yingxiang Liu, Peiwen Feng, Xing Wei, Hongyu Xu, Mengying Yu, Lei Zhang, Weijie Hao, Zekun Guo.
      Timely and accurate translation of maternal mRNA is essential for oocyte maturation and early embryonic development. Previous studies have highlighted the importance of Primordial Germ cell 7 (PGC7) as a maternal factor in maintaining DNA methylation of maternally imprinted loci in zygotes. However, it is still unknown whether PGC7 is involved in the regulation of Maternal mRNA Translation. In this study, we have identified that PGC7-AKT1-YBX1 axis is involved in promoting the translation of maternal mRNAs. PGC7 not only sustains AKT1 activity by counteracting PP2A dephosphorylation and facilitating PDK1-AKT1 binding but also assists AKT1 in phosphorylating the translation inhibitor YBX1. In the absence of PGC7, despite increased PIK3CA expression and AKT1 phosphorylation, AKT1 is unable to phosphorylate YBX1. PGC7 facilitates the interaction between AKT1 and YBX1, enhancing YBX1-Serine 100 phosphorylation, which leads to YBX1 dissociation from eIF4E, thereby activating the translation of maternal Cyclin B1 and YAP1. The findings demonstrate the indispensability of PGC7 for translation activation in mammalian oocytes and provide a potential network regulated by PGC7 in early oogenesis.
    Keywords:  AKT1; Maternal mRNA translation; Oocyte; PGC7; YBX1
    DOI:  https://doi.org/10.1186/s12964-024-01976-1
  3. J Cell Biol. 2025 Mar 03. pii: e202408092. [Epub ahead of print]224(3):
    Identification of the Polo-like kinase substrate required for homologous synapsis.
    Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim.
      The synaptonemal complex (SC) is a zipper-like protein structure that aligns homologous chromosome pairs and regulates recombination during meiosis. Despite its conserved appearance and function, how synapsis occurs between chromosome axes remains elusive. Here, we demonstrate that Polo-like kinases (PLKs) phosphorylate a single conserved residue in the disordered C-terminal tails of two paralogous SC subunits, SYP-5 and SYP-6, to establish an electrostatic interface between the SC central region and chromosome axes in C. elegans. While SYP-5/6 phosphorylation is dispensable for the ability of SC proteins to self-assemble, local phosphorylation by PLKs at the pairing center is crucial for SC elongation between homologous chromosome axes. Additionally, SYP-5/6 phosphorylation is essential for asymmetric SC disassembly and proper PLK-2 localization after crossover designation, which drives chromosome remodeling required for homolog separation during meiosis I. This work identifies a key regulatory mechanism by which localized PLK activity mediates the SC-axis interaction through phosphorylation of SYP-5/6, coupling synapsis initiation to homolog pairing.
    DOI:  https://doi.org/10.1083/jcb.202408092
  4. Int J Mol Sci. 2024 Dec 03. pii: 13002. [Epub ahead of print]25(23):
    Genetic Abnormalities of Oocyte Maturation: Mechanisms and Clinical Implications.
    Giorgio Maria Baldini, Daniele Ferri, Antonio Malvasi, Antonio Simone Laganà, Antonella Vimercati, Miriam Dellino, Domenico Baldini, Giuseppe Trojano.
      Genetic anomalies in oocyte maturation present significant fertility and embryonic development challenges. This review explores the intricate mechanisms of nuclear and cytoplasmic maturation, emphasizing the genetic and molecular factors contributing to oocyte quality and competence. Chromosomal mutations, errors in segregation, genetic mutations in signaling pathways and meiosis-related genes, and epigenetic alterations are discussed as critical contributors to oocyte maturation defects. The role of mitochondrial defects, maternal mRNA dysregulation, and critical proteins such as NLRP14 and BMP6 are highlighted. Understanding these genetic factors is crucial for improving diagnostic approaches and therapeutic interventions in reproductive medicine, particularly for couples encountering recurrent in vitro fertilization failures. This review will explore how specific genetic mutations impact fertility treatments and reproductive success by examining the intricate oocyte maturation process. We will focus on genetic abnormalities that may disrupt the oocyte maturation pathway, discussing the underlying mechanisms involved and considering their potential clinical implications for enhancing fertility outcomes.
    Keywords:  ICSI; IVF; genetic abnormalities; oocyte maturation
    DOI:  https://doi.org/10.3390/ijms252313002
  5. Front Cell Dev Biol. 2024 ;12 1475912
    Low-input CUT&Tag for efficient epigenomic profiling of zebrafish stage I oocytes.
    Qianwen Zheng, Xiaotong Wu, Xin Li, Xianming Mo, Bo Xiang, Jing Chen.
      Histone modification signatures mark sites of transcriptional regulatory elements and regions of gene activation and repression. These sites vary among cell types and undergo dynamic changes during development and in diseases. Oocytes produce numerous maternal factors essential for early embryonic development, which are significantly influenced by epigenetic modifications. The profiling of epigenetic modifications during oogenesis remains uniquely challenging due to the presence of numerous tightly wrapped granulosa cells. Here, we successfully established a low-input CUT&Tag (Cleavage Under Targets and Tagmentation) method tailored for zebrafish stage I oocytes. This advanced technique enables high-resolution profiling of histone modifications and DNA-binding proteins, critical for understanding chromatin dynamics in developing oocytes. In this study, we detailed the workflow for this technique, including the isolation of pure stage I oocytes without somatic cells, library construction and quality monitoring. Our results demonstrate the method's efficacy by identifying distinct histone modification patterns and analyzing differentially expressed genes in oocytes with and without granulosa cells. We also successfully profiled divergent histone modifications in oocytes derived from wild-type and huluwa mutants. These advancements overcome technical challenges in epigenetic research on zebrafish oocytes and establish a solid foundation for exploring the epigenetic regulatory mechanisms of maternal contribution.
    Keywords:  Cut&Tag; epigentic; histone modifications; oocyte; zebrafish
    DOI:  https://doi.org/10.3389/fcell.2024.1475912
  6. Aging Cell. 2024 Dec 15. e14449
    Age-associated accumulation of RAB9 disrupts oocyte meiosis.
    Min Gao, Fang Wang, Tengteng Xu, Yanling Qiu, Tianqi Cao, Simiao Liu, Wenlian Wu, Yitong Zhou, Haiying Liu, Fenghua Liu, Junjiu Huang.
      The critical role of some RAB family members in oocyte meiosis has been extensively studied, but their role in oocyte aging remains poorly understood. Here, we report that the vesicle trafficking regulator, RAB9 GTPase, is essential for oocyte meiosis and aging in humans and mice. RAB9 was mainly located at the meiotic spindle periphery and cortex during oocyte meiosis. In humans and mice, we found that the RAB9 protein level were significantly increased in old oocytes. Age-related accumulation of RAB9 inhibits first polar body extrusion and reduces the developmental potential of oocytes. Further studies showed that increased Rab9 disrupts spindle formation and chromosome alignment. In addition, Rab9 overexpression disrupts the actin cap formation and reduces the cortical actin levels. Mechanically, Rab9-OE increases ROS levels, decreases mitochondrial membrane potential, ATP content and the mtDNA/nDNA ratio. Further studies showed that Rab9-OE activates the PINK1-PARKIN mitophagy pathway. Importantly, we found that reducing RAB9 protein expression in old oocytes could partially improve the rate of old oocyte maturation, ameliorate the accumulation of age-related ROS levels and spindle abnormalities, and partially rescue ATP levels, mtDNA/nDNA ratio, and PINK1 and PARKIN expression. In conclusion, our results suggest that RAB9 is required to maintain the balance between mitochondrial function and meiosis, and that reducing RAB9 expression is a potential strategy to ameliorate age-related deterioration of oocyte quality.
    Keywords:  RAB9; aging; meiosis; mitochondrial function; oocyte
    DOI:  https://doi.org/10.1111/acel.14449
  7. Int J Biol Macromol. 2024 Dec 16. pii: S0141-8130(24)09638-7. [Epub ahead of print] 138827
    The GPER is an important factor through which somatic cells regulate oocyte maternal mRNA translation and developmental competence.
    Hui Zhang, Chan Li, Sihai Lu, Hao Wu, Jingmei Li, Qingyang Liu, Yutong Yan, Yaju Tang, Rui Xu, Xiaoe Zhao, Menghao Pan, Qiang Wei, Sha Peng, Baohua Ma.
      The G protein-coupled estrogen receptor (GPER) plays a crucial role in various biological processes, but its regulation of oocyte meiosis remains unclear. In this study, we generated a Gper1 knockout in growing oocytes using Zp3-Cre, revealing that GPER is essential for oocyte maturation and embryo development. RNA-seq analysis indicated that GPER deficiency significantly altered the oocyte transcriptome and disrupted mRNA translation. Immunoprecipitation mass spectrometry revealed that GPER directly interacts with HSP90 and modulates the ERK1/2 and PI3K-AKT signaling pathways, which are vital for enhancing maternal mRNA translation and developmental potential. We also found that cumulus cell-derived GPER-positive vesicles and delivered to oocytes through a RAB11A-dependent pathway. RAB11A facilitates GPER recycling, preventing its degradation in late endosomes and promoting its plasma membrane localization. Moreover, epidermal growth factor (EGF) improves GPER expression in cumulus cells by upregulating RAB11A, thereby enhancing the exocytosis of recycling vesicles. Knockdown of Rab11a severely reduced GPER-positive vesicles in oocytes, impairing spindle morphogenesis and meiosis. Our findings highlight the critical role of somatic cell signals in regulating maternal mRNA translation and oocyte quality for embryonic development.
    Keywords:  G-protein-coupled estrogen receptor; Meiosis; Oocyte; Translation; Vesicle
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.138827
  8. Curr Biol. 2024 Dec 16. pii: S0960-9822(24)01499-4. [Epub ahead of print]34(24): R1228-R1230
    Germ cell development: Anchoring and pulling forces shape germline cyst construction.
    Yaniv M Elkouby.
      A new study reports a 'tug-of-war' mechanism in mouse germline cyst formation, where cell motility and intercellular bridges balance fragmentation and stabilization of the cyst. These dynamic and opposing forces that anchor and pull cells apart shape cyst construction, advancing our understanding of mammalian oogenesis and reproduction.
    DOI:  https://doi.org/10.1016/j.cub.2024.10.072
  9. Reprod Fertil Dev. 2024 Dec;pii: RD24131. [Epub ahead of print]37
    Identifying the composition of large vesicles in the cytoplasm of oocytes.
    Karen L Reader, Isabella G Pratt, Georgia L Lawson, Robert J Woolley.
      Context Oocyte vesicles, or vacuoles, have been described using transmission electron microscopy in most species. In sheep and cow oocytes, vesicles constitute up to 30% of the cytoplasm, their volume decreases during maturation and is lower in poorer quality oocytes, suggesting they are important for oocyte competence. However, the composition and function of these organelles is unknown. Aim This study aimed to ascertain the content of oocyte vesicles and examine the effect of different fixation methods on the size and preservation of these organelles. Methods Sheep oocytes were centrifuged to segregate organelles then stained with organelle-specific fluorescent dyes (Nile Red, LysoTracker, Fluo-4-AM and TMRM) and imaged by live cell confocal microscopy. The oocytes were fixed with either glutaraldehyde or paraformaldehyde and prepared for electron microscopy to confirm the distribution of organelles and compare ultrastructure and organelle size. Key results Nile Red staining has identified that vesicles contain lipid that is different to that in the osmium-stained lipid droplets observed by electron microscopy. Lipid droplets and vesicles were significantly smaller when prepared for electron microscopy compared to live cell imaging. Organelles were less likely to be fully segregated following centrifugation in oocytes prior to maturation (20%) compared to oocytes after maturation (77%; P Conclusions Oocyte vesicles are lipid storing organelles that may be important for oocyte quality. Implications This study highlights the importance of lipid for oocyte quality and the need for further research to identify the optimal fatty acid content for in vitro maturation media and oocyte competence.
    DOI:  https://doi.org/10.1071/RD24131
  10. Dev Biol. 2024 Dec 14. pii: S0012-1606(24)00276-8. [Epub ahead of print]
    Transcriptomic analysis and epigenetic regulators in human oocytes at different stages of oocyte meiotic maturation.
    Carla Caniçais, Daniel Sobral, Sara Vasconcelos, Mariana Cunha, Alice Pinto, Joana Mesquita Guimarães, Fátima Santos, Alberto Barros, Sofia Dória, C Joana Marques.
      Human oocytes are highly specialized cells with the capacity to store and regulate mRNAs during oocyte maturation, in preparation for post-fertilization steps. Here we performed single-oocyte transcriptomic analysis of human oocytes in three meitoic maturation stages - Germinal Vesicle (GV; n=6), Metaphase I (MI; n=6) and Metaphase II (MII; n=7). Single-oocyte transcriptomic analysis revealed that the total number of expressed genes progressively decreased from GV to MII stages, with 9660 genes being transcribed in GV, 8734 in MI and 5889 in MII. The same tendency was observed for the number of uniquely expressed genes, with 1328 uniquely expressed genes in GV, 401 in MI and 72 in MII. GO analysis of the uniquely expressed genes showed distinct terms in GV oocytes such as transferase activity, organonitrogen compound metabolic process and ncRNA processing. Analysis of Differentially Expressed Genes (DEGs) between the three maturation stages revealed 1165 DEGs between GV and MII oocytes, with 635 being upregulated and 528 downregulated, 42 DEGs between GV and MI, with 38 being upregulated and 4 downregulated, and no significant changes in gene expression between MI and MII oocytes. Comprehensive analysis of epigenetic regulators showed high expression of several histone-modifying enzymes, namely deacetylases, acetylases, lysine demethylases and methyltransferases, and DNA methylation regulators, namely the maintenance methyltransferase DNMT1 and its co-regulators DPPA3 and UHRF1. Some of these epigenetic regulators were differentially expressed between maturation stages, namely SIRT3, SIRT6, KDM3AP1, KMT2E, DNMT1, DPPA3 and the MEST and RASGRF1 imprinted genes. Our study contributes with important information on the transcriptional landscape of human oocytes in different stages of meiotic maturation, providing important insights into candidate biomarkers of human oocyte quality.
    Keywords:  Epigenetics; Meiosis; Oocytes; Oogenesis; RNA-Seq; Transcriptome
    DOI:  https://doi.org/10.1016/j.ydbio.2024.12.004
  11. bioRxiv. 2024 Dec 05. pii: 2024.12.04.626831. [Epub ahead of print]
    The Effects of Heat Stress on the Ovary, Follicles and Oocytes: A Systematic Review.
    Luhan T Zhou, Dilan Gokyer, Krystal Madkins, Molly Beestrum, Daniel E Horton, Francesca E Duncan, Elnur Babayev.
      Climate change is driving significant environmental changes with profound implications for human health, including fertility. While the detrimental effects of heat on spermatogenesis are well-documented, the impact of elevated temperatures on ovaries and female fertility remains less explored. This review systematically examines the literature on heat stress (HS) effects on mammalian ovaries, follicles, and oocytes. Evidence from mammalian models indicates that HS significantly impairs ovarian function, disrupting hormone profiles, reducing ovarian size and weight, altering histology, decreasing granulosa cell viability, and compromising oocyte quality. Efforts to develop strategies and substances to mitigate these adverse effects are ongoing, but further research into the underlying mechanisms is urgently needed.
    Keywords:  egg; fertility; gamete; granulosa cells; increased temperature; ovarian reserve; reproduction
    DOI:  https://doi.org/10.1101/2024.12.04.626831
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