bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–12–14
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Cyst-independent oocyte phagocytosis builds the female reproductive reserve in mice.
  2. Newly Evolved Endogenous Retroviruses Prime the Ovarian Reserve for Activation.
  3. The oocyte zinc transporter Slc39a10/Zip10 is a regulator of zinc sparks during fertilization in mice.
  4. Natural degradation of RNA polymerase II is essential for oocyte chromatin reorganization and maternal-to-zygotic transition.
  5. Cell size reduction drives spindle scaling but not chromosome segregation in C. elegans.
  6. Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification.
  7. Somatic Cells Induce Male-Biased Translational Activity in the Germline of Drosophila melanogaster.
  8. Roles of the zona pellucida in gamete fusion and of the perivitelline space in blocking polyspermy in mice.
  9. OTX2 controls chromatin accessibility to direct somatic versus germline differentiation.
  10. The Influence of Drosophila Spire and Myosin V During Mid-Oogenesis Is Independent of Their Direct Interaction.
  11. Feed-forward loops by NR5A2 ensure robust gene activation during pre-implantation development.
  12. Overexpression of CCNK Leads to Early Resumption of Meiosis in Mouse Oocytes.
  13. Oocyte selection: a tale of individualism, dominance and sacrifice.
  1. EMBO Rep. 2025 Dec 08.
    Cyst-independent oocyte phagocytosis builds the female reproductive reserve in mice.
    Yan Zhang, Yingnan Bo, Kaixin Cheng, Ge Wang, Lu Mu, Jing Liang, Lingyu Li, Kaiying Geng, Xuebing Yang, Xindi Hu, Wenji Wang, Longzhong Jia, Xueqiang Xu, Jingmei Hu, Chao Wang, Fengchao Wang, Yuwen Ke, Guoliang Xia, Hua Zhang.
      During ovariogenesis, more than two-thirds of germ cells are sacrificed to improve the quality of the remaining oocytes. However, the detailed mechanisms behind this selection process are not fully understood in mammals. Here, we developed a high-resolution, four-dimensional ovariogenesis imaging system to track the progression of oocyte fate determination in live mouse ovaries. Through this, we identified a cyst-independent oocyte phagocytosis mechanism that plays a key role in determining oocyte survival. We found that oocytes act as individual cells, rather than connected cyst structures, during ovarian reserve construction. In this process, dominant oocytes capture and absorb cell debris from sacrificed oocytes to enrich their cytoplasm and support their survival. Single-cell sequencing indicated that the sacrificed oocytes are regulated by autophagy. When oocyte sacrifice was inhibited using autophagy inhibitors, the pool of surviving oocytes expanded, but they failed to fully develop and contribute to fertility. Our study suggests that mammals have evolved a cyst-independent selection system to improve oocyte quality, which is essential for sustaining a long reproductive lifespan.
    Keywords:  Female Fertility; Live Organ Imaging; Oocyte Phagocytosis; Oocytes; Ovarian Reserve
    DOI:  https://doi.org/10.1038/s44319-025-00663-7
  2. Res Sq. 2025 Dec 03. pii: rs.3.rs-8081066. [Epub ahead of print]
    Newly Evolved Endogenous Retroviruses Prime the Ovarian Reserve for Activation.
    Yasuhisa Munakata, Mengwen Hu, Raissa Dani, Naokazu Inoue, Richard Schultz, Satoshi Namekawa.
      Female mammals are born with a finite pool of non-growing oocytes (NGOs) housed in primordial follicles, which form the ovarian reserve that determines reproductive lifespan. Mechanisms underlying the reserve's long-term maintenance and subsequent follicular activation remain elusive. Using total RNA sequencing and de novo transcriptome assembly, we first captured the comprehensive oocyte transcriptome across perinatal oogenesis in mice. We show that NGOs establish accessible chromatin at gene regulatory elements-including promoters and enhancers-partly driven by newly evolved endogenous retroviruses (ERVs). In NGOs, epigenetic priming for follicular activation involves prior loading of transcription factors TCF3 and TCF12 and non-phosphorylated form of RNA polymerase II at these sites. This primed state is counteracted by repression via Polycomb Repressive Complex 1-mediated H2AK119 ubiquitylation. We propose that ERV-mediated epigenetic priming underlies the ovarian reserve's long-term maintenance and establishes a transcriptionally competent yet repressive configuration that enables rapid gene activation upon oocyte growth.
    DOI:  https://doi.org/10.21203/rs.3.rs-8081066/v1
  3. Elife. 2025 Dec 11. pii: RP106616. [Epub ahead of print]14
    The oocyte zinc transporter Slc39a10/Zip10 is a regulator of zinc sparks during fertilization in mice.
    Atsuko Kageyama, Narumi Ogonuki, Takuya Wakai, Takafumi Namiki, Yui Kawata, Manabu Ozawa, Yasuhiro Yamada, Toshiyuki Fukada, Atsuo Ogura, Rafael Fissore, Naomi Kashiwazaki, Junya Ito.
      In all vertebrates studied to date, a rise(s) in intracellular calcium is indispensable for successful fertilization and further embryonic development. Recent studies demonstrated that zinc is ejected to the extracellular milieu, the 'zinc spark', and follows the first few calcium rises of fertilization. However, the role of the zinc sparks in fertilization and development, as well as the supporting influx mechanism(s), remains unknown. In this study, we focused on zinc transporters Slc39a10/Zip10 which were expressed in mouse oocytes through follicular development and investigated the oocyte-specific deficient mice for Slc39a10/Zip10 (Slc39a10 cKO: Slc39a10flox/flox Gdf9Cre/+). Slc39a10 mRNA or SLC39A10/ZIP10 protein was expressed throughout folliculogenesis in the oocyte or plasma membrane, respectively. The number of ovulated oocytes was examined in Slc39a10 cKO mice, and no change from the number of oocytes was observed. Slc39a10 cKO oocytes decreased zinc level in the oocytes but did not affect maturation and metaphase II spindle formation. Fertilization-induced calcium oscillations were present in Slc39a10 cKO oocytes, but zinc sparks were not observed. Despite other events of egg activation proceeding normally in Slc39a10 cKO oocytes, embryo development into 4 cells and beyond was compromised. We show here for the first time that the zinc transporter ZIP10 contributes to zinc homeostasis in oocytes and embryos, highlighting the role of labile zinc ions in early development.
    Keywords:  cell biology; developmental biology; embryo development; fertilization; mammals; mouse; zinc homeostasis; zinc spark
    DOI:  https://doi.org/10.7554/eLife.106616
  4. Nat Commun. 2025 Dec 12.
    Natural degradation of RNA polymerase II is essential for oocyte chromatin reorganization and maternal-to-zygotic transition.
    Jing Wang, Wang Li, Jing Guo, Xiaoming Xu, Ge Lin, Bin Li, Chun So.
      The final step of oocyte growth, which reorganizes chromatin from the non-surrounded nucleolus (NSN) to the surrounded nucleolus (SN) configuration is essential for embryonic development after meiotic maturation and fertilization. The underlying mechanisms remain unknown. We identify RNA polymerase II (RNAPII) degradation as the key driver of this process. Inhibitors that trigger RNAPII degradation, but not nucleoside-based transcription inhibitors, induce NSN-to-SN transition in oocytes. By establishing miniTrim-Away for nuclear proteins and using segregase and proteasome inhibitors, we demonstrate that RNAPII degradation is necessary and sufficient for NSN-to-SN transition. Further experiments reveal that RNAPII degradation results in a global collapsing force and a local attractive force required for the transition to SN configuration. Finally, embryos derived from NSN oocytes have aberrant RNAPII levels and localization, and are defective in maternal-to-zygotic transition. Our study elucidates the mechanistic framework of oocyte chromatin reorganization and presents a strategy for inducing fully grown oocyte nuclei.
    DOI:  https://doi.org/10.1038/s41467-025-67476-z
  5. Res Sq. 2025 Dec 01. pii: rs.3.rs-7923379. [Epub ahead of print]
    Cell size reduction drives spindle scaling but not chromosome segregation in C. elegans.
    Chukwuebuka William Okafornta, Reza Farhadifar, Gunar Fabig, Hai-Yin Wu, Maria Köckert, Martin Vogel, Daniel Baum, Robert Haase, Michael Shelley, Daniel Needleman, Thomas Müller-Reichert.
      How embryos adapt their internal cellular machinery to reductions in cell size during development remains a fundamental question in cell biology 1-11 . Here, we use high-resolution lattice light-sheet fluorescence microscopy and automated image analysis to quantify lineage-resolved mitotic spindle and chromosome segregation dynamics from the 2- to 64-cell stages in Caenorhabditis elegans embryos. While spindle length scales with cell size across both wild-type and size-perturbed embryos, chromosome segregation dynamics remain largely invariant, suggesting that distinct mechanisms govern these mitotic processes. Combining femtosecond laser ablation 12,13 with large-scale electron tomography 14 , we find that central spindle microtubules mediate chromosome segregation dynamics and remain uncoupled from cell size across all stages of early development. In contrast, spindle elongation is driven by cortically anchored motor proteins and astral microtubules, rendering it sensitive to cell size 12,13,15-17 . Incorporating these experimental results into an extended stoichiometric model for both the spindle and chromosomes, we find that allowing only cell size and microtubule catastrophe rates to vary reproduces elongation dynamics across development. The same model also accounts for centrosome separation and pronuclear positioning in the one-cell C. elegans embryo 18 , spindle-length scaling across nematode species spanning ~100 million years of divergence 17 , and spindle rotation in human cells 19 . Thus, a unified stoichiometric framework provides a predictive, mechanistic account of spindle and nuclear dynamics across scales and species.
    DOI:  https://doi.org/10.21203/rs.3.rs-7923379/v1
  6. Elife. 2025 Dec 08. pii: RP101140. [Epub ahead of print]13
    Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification.
    Adiyant Lamba, Meng Zhu, Maciej Meglicki, Sylwia Czukiewska, Lakshmi Balasubramaniam, Ron Hadas, Nina Weishaupt, Ekta M Patel, Yu Hua Kavanagh, Ran Wang, Naihe Jing, Magdalena Zernicka-Goetz.
      The first lineage allocation in mouse and human embryos separates the inner cell mass (ICM) from the outer trophectoderm (TE). This symmetry-breaking event is executed through polarization of cells at the 8 cell stage and subsequent asymmetric divisions, generating polar (TE) and apolar (ICM) cells. Here, we show that mouse embryo polarization is unexpectedly asynchronous. Cells polarizing at the early and late 8 cell stage have distinct molecular and morphological properties that direct their following lineage specification, with early polarizing cells being biased towards producing the TE lineage. More recent studies have also implicated heterogeneities between cells prior to the 8 cell stage in the first lineage allocation: cells exhibiting reduced methyltransferase CARM1 activity at the 4 cell stage are predisposed towards the TE fate. Here, we demonstrate that reduced CARM1 activity and upregulation of its substrate BAF155 promote early polarization and TE specification. These findings provide a link between asymmetries at the 4 cell stage and polarization at the 8 cell stage, mechanisms of the first lineage allocation that had been considered separate.
    Keywords:  cell fate; developmental biology; mouse; mouse embryo development; polarity; preimplantation development
    DOI:  https://doi.org/10.7554/eLife.101140
  7. Dev Growth Differ. 2025 Dec 08.
    Somatic Cells Induce Male-Biased Translational Activity in the Germline of Drosophila melanogaster.
    Masaki Masukawa, Ryoma Ota, Kana Innami, Satoru Kobayashi.
      The germline of Drosophila melanogaster originates from primordial germ cells (PGCs). The sex of PGCs is determined during mid-to-late embryogenesis, and PGCs subsequently begin to differentiate into eggs or sperm. Several genes involved in the sex determination of PGCs have been identified, but the mechanisms underlying sex differentiation remain unclear. To clarify these mechanisms, identifying the sex-specific differences in PGCs and elucidating how these differences arise is necessary. We previously found that translational activity in PGCs was higher in males than in females at the late embryonic stage. However, it remains unclear when male-biased translational activity is initiated and the mechanisms that induce this bias are unknown. Here, we show that male-biased translational activity in PGCs is observed from the stage when the JAK/STAT pathway, a known masculinizing pathway in PGCs, is activated. Furthermore, this male-biased translational activity depended on the sex of the surrounding somatic cells. Moreover, the JAK/STAT pathway did not affect male-biased translational activity in embryonic PGCs, although it did affect larval germline cells. These findings suggest that embryonic PGCs respond to previously unidentified signals, rather than to the JAK/STAT pathway, from somatic cells, which in turn induces male-biased translational activity.
    Keywords:  Janus kinases; germ cells; gonads; protein biosynthesis; sex differentiation
    DOI:  https://doi.org/10.1111/dgd.70035
  8. EMBO Rep. 2025 Dec 08.
    Roles of the zona pellucida in gamete fusion and of the perivitelline space in blocking polyspermy in mice.
    Yaëlle Dubois, Sophie Favier, Nathan Martin-Fornier, Adrien Freyss, Mohyeddine Omrane, David Stroebel, Eric Perez, Sandrine Barbaux, Ahmed Ziyyat, Nicolas Rodriguez, Christine Gourier.
      The mechanisms regulating gamete fusion and preventing polyspermy in mammalian fertilization remain incompletely understood. This study combines real-time imaging, confocal microscopy and statistical analysis to investigate fertilization and polyspermy prevention dynamics in mice. By tracking the behavior of over one hundred spermatozoa entering the perivitelline space of oocytes, we dissect the respective contributions of oocyte structures (zona pellucida (ZP), perivitelline space (PVS), oolemma) and sperm components (head, flagellum) to fertilization and polyspermy prevention. We find that fertilization requires specific sperm head movements on the oolemma, driven by flagellar beating and facilitated by trapping the flagellum in the ZP, revealing a novel role for this structure. Our kinetic analysis characterizes a slow "penetration block" that gradually limits sperm entry into the PVS and a faster "fusion block" that prevents further fusion events. As the penetration block becomes significant after the fusion block is established, only the latter effectively prevents polyspermy in mice. We propose that it acts through neutralization of excess sperm in the PVS by oocyte-derived proteins CD9 and JUNO coating non-fertilizing spermatozoa.
    Keywords:  Gamete Fusion; Mammalian Fertilization; Polyspermy Prevention; Real Time Imaging; Sperm Flagellum Beating
    DOI:  https://doi.org/10.1038/s44319-025-00670-8
  9. EMBO Rep. 2025 Dec 08.
    OTX2 controls chromatin accessibility to direct somatic versus germline differentiation.
    Elisa Barbieri, Ian Chambers.
      The choice between somatic and germline fates is essential for species survival. This choice occurs in embryonic epiblast cells, as these cells are competent for both somatic and germline differentiation. The transcription factor OTX2 regulates this process, as Otx2-null epiblast-like cells (EpiLCs) form primordial germ cell-like cells (PGCLCs) with enhanced efficiency. Yet, how OTX2 achieves this function is not fully characterised. Here we show that OTX2 controls chromatin accessibility at specific chromatin loci to enable somatic differentiation. CUT&RUN for OTX2 and ATAC-seq in wild-type and Otx2-null embryonic stem cells and EpiLCs identifies regions where OTX2 binds and opens chromatin. Enforced OTX2 expression maintains accessibility at these regions and also induces opening of ~4000 somatic-associated regions in cells differentiating in the presence of PGC-inducing cytokines. Once cells have acquired germline identity, these additional regions no longer respond to OTX2 and remain closed. Our results indicate that OTX2 works in cells with dual competence for somatic and germline differentiation to increase accessibility of somatic regulatory regions and induce the somatic fate at the expense of the germline.
    Keywords:  Chromatin Accessibility; Formative Pluripotency; Germline; OTX2
    DOI:  https://doi.org/10.1038/s44319-025-00622-2
  10. Cytoskeleton (Hoboken). 2025 Dec 08.
    The Influence of Drosophila Spire and Myosin V During Mid-Oogenesis Is Independent of Their Direct Interaction.
    Joseph Y Ong, Hannah M Bailey, Emma Carley, Michelle Panzica, Merin Rixen, Neil Billington, Rong Liu, Margot E Quinlan.
      Cooperativity between cytoskeletal proteins is crucial for spatiotemporal coordination in biological processes, like oogenesis. In mammalian and Drosophila oogenesis, proper assembly and function of actin networks require coordination between actin assembly factors Spire and formins, as well as actin-associated proteins like myosins and Rab GTPases. Here, we investigate the interaction between Spire and Myosin V (MyoV) in Drosophila oogenesis. We combine in vitro biochemical assays with immunofluorescence and genetics to probe the interaction and its impact on polarity establishment and the actin mesh that fills the oocyte during mid-oogenesis. Expressed Spire and MyoV constructs colocalize in punctae during mid oogenesis, with considerable enrichment near the oocyte cortex. Purified constructs interact directly in vitro, and we find that Spire can weakly activate MyoV ATPase activity. Cytoplasmic flows, critical for polarity establishment, are faster and more coordinated in the absence of MyoV, although not to the extent of fast streaming. This intermediate streaming has not been observed before. Interestingly, this MyoV-dependent change in ooplasm dynamics is sensitive to Spire levels. Despite this interplay, the actin mesh and polarity establishment appear normal when binding mutants of Spire and MyoV are expressed in the Drosophila germline. These findings suggest that direct interaction between Spire and MyoV is not essential for their primary roles at this stage of development.
    Keywords:   Drosophila ; actin; myosin V; oogenesis; spire
    DOI:  https://doi.org/10.1002/cm.70080
  11. Development. 2025 Dec 08. pii: dev.205059. [Epub ahead of print]
    Feed-forward loops by NR5A2 ensure robust gene activation during pre-implantation development.
    Wataru Kobayashi, Siwat Ruangroengkulrith, Eda Nur Arslantas, Adarsh Mohanan, Kikuë Tachibana.
      Pioneer transcription factors are crucial for regulating zygotic genome activation and cell differentiation during mouse pre-implantation development. However, how pioneer factors function collectively to regulate early development remains poorly understood. Here, we determined the chromatin binding profiles of the pioneer factor NR5A2 during the totipotency-to-pluripotency transition and identified KLF and GATA family transcription factors as key co-regulators. NR5A2 regulates the expression of Klf5 and Gata6, whose proteins in turn act as co-regulators of NR5A2 to promote development. Mechanistically, KLF5 contributes to H3K27ac deposition at genomic regions co-occupied by NR5A2. NR5A2 also regulates Xist expression, either directly or indirectly, through its role in co-binding with GATA factors and up-regulating their expression. In vitro assays revealed that NR5A2 binds to nucleosomes with KLF5 and GATA6, suggesting that these pioneer factors can simultaneously bind to chromatin. Our findings provide evidence for a feed-forward regulatory mechanism by which NR5A2 activates expression of lineage-determining factors and these, together with NR5A2, subsequently co-bind nucleosomes to ensure robust gene activation during pre-implantation development.
    Keywords:  Lineage-determining factor; Nuclear receptor; Pioneer transcription factor; Pre-implantation development; Transcriptional regulation
    DOI:  https://doi.org/10.1242/dev.205059
  12. Mol Reprod Dev. 2025 Dec;92(12): e70075
    Overexpression of CCNK Leads to Early Resumption of Meiosis in Mouse Oocytes.
    Yuan-Hong Xu, Si-Min Sun, Bing-Wang Zhao, Jia-Ni Guo, Xue-Mei Yang, Yi-Ke Lu, Yi-Na Zhang, Ji Ding, Zhen-Bo Wang.
      The synthesis and degradation of Cyclins are critical for cell cycle progression. Cyclin K (CCNK), a member of the Cyclin family, is known to regulate transcriptional elongation and the MAPK signaling pathway by binding to CDK12/13. While CCNK has been extensively studied in cancers, its roles in oocyte maturation remains unclear. In this study, we found that overexpression of CCNK accelerates the resumption of meiosis in oocytes. This effect is primarily attributed to the early nuclear entry of Cyclin B1 (CCNB1) and the premature activation of maturation promoting factor. These findings suggest that CCNK plays a vital role in the process of oocyte maturation, and its dysregulation could disrupt the normal progression of meiosis.
    Keywords:  CCNK; MPF; cyclin; meiosis; oocytes
    DOI:  https://doi.org/10.1002/mrd.70075
  13. EMBO Rep. 2025 Dec 08.
    Oocyte selection: a tale of individualism, dominance and sacrifice.
    Katja Wassmann.
      
    DOI:  https://doi.org/10.1038/s44319-025-00665-5
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