bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–10–05
eight papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Induction of experimental cell division to generate cells with reduced chromosome ploidy.
  2. Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation.
  3. eIF4E assembly into C. elegans germ granules is essential for its repressive function.
  4. C. elegans kinesin 1 regulates meiotic spindle size.
  5. The DND1-NANOS3 complex shapes the primordial germ cell transcriptome via a heptanucleotide sequence in mRNA 3' UTRs.
  6. Centrosomes regulate pronuclear apposition ensuring parental genome unification in cattle.
  7. CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve.
  8. Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.
  1. Nat Commun. 2025 Sep 30. 16(1): 8340
    Induction of experimental cell division to generate cells with reduced chromosome ploidy.
    Nuria Marti Gutierrez, Aleksei Mikhalchenko, Maria Shishimorova, Daniel Frana, Crystal Van Dyken, Ying Li, Hong Ma, Amy Koski, Dan Liang, Sang-Goo Lee, Daniel Eyberg, Zahra Safaei, Eunju Kang, Yeonmi Lee, Thomas O'Leary, David Lee, Sacha Krieg, Diana Wu, Elizabeth Rubin, Paula Amato, Shoukhrat Mitalipov.
      Somatic cell nuclear transfer (SCNT) enables the direct reprogramming of somatic cells into functional oocytes, albeit with a diploid genome. To address ploidy reduction, we investigated an experimental reductive cell division process, termed mitomeiosis, wherein non-replicated (2n2c) somatic genomes are prematurely forced to divide following transplantation into the metaphase cytoplasm of enucleated human oocytes. However, despite fertilization with sperm, SCNT oocytes remained arrested at the metaphase stage, indicating activation failure. Artificial activation using a selective cyclin-dependent kinase inhibitor successfully bypassed this arrest, inducing the segregation of somatic chromosomes into a zygotic pronucleus and a polar body. Comprehensive chromosome tracing via sequencing revealed that homologous chromosome segregation occurred randomly and without crossover recombination. Nonetheless, an average of 23 somatic chromosomes were retained within the zygote, demonstrating the feasibility of experimentally halving the diploid chromosome set. Fertilized human SCNT oocytes progressed through normal embryonic cell divisions, ultimately developing into embryos with integrated somatic and sperm-derived chromosomes. While our study demonstrates the potential of mitomeiosis for in vitro gametogenesis, at this stage it remains just a proof of concept and further research is required to ensure efficacy and safety before future clinical applications.
    DOI:  https://doi.org/10.1038/s41467-025-63454-7
  2. iScience. 2025 Oct 17. 28(10): 113474
    Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation.
    Jonathan A DiRusso, Lingyu Zhan, Yu Tao, Allison L Wang, Xinyu Xiang, Alexander C Robbins, Azra J Cruz, Wanlu Liu, Amander T Clark.
      Mammalian primordial germ cells (PGCs) are embryonic precursors to the adult germline and must facilitate high-fidelity transfer of genomic material from one generation to the next. Transposable elements (TEs) represent an ongoing threat to genomic fidelity and are therefore tightly controlled during embryonic germline development. Here, we find that some TEs change in accessibility during normal PGC differentiation, while others are constitutively repressed by tripartite motif-containing 28 (TRIM28), a master TE regulator. We find that TRIM28 itself is regulated in a sex-specific manner and represses sex-specific TEs. In both testicular and ovarian PGCs, TRIM28 protects against upregulation of 2-cell (2C)-associated genes, dysregulation of PGC differentiation, and incomplete activation of DAZL. This perturbs testicular and ovarian PGCs differently, with testicular PGCs failing to differentiate in embryonic life while ovarian PGCs inefficiently enter meiosis leading to a diminished ovarian reserve by the onset of sexual maturity.
    Keywords:  Cell biology; Epigenetics; Molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2025.113474
  3. bioRxiv. 2025 Sep 25. pii: 2025.09.24.678427. [Epub ahead of print]
    eIF4E assembly into C. elegans germ granules is essential for its repressive function.
    Carmen Herrera Sandoval, Christopher Borchers, Boyoon Yang, Becky Boyd, Heather A Hundley, Scott T Aoki.
      Metazoan germ cells form intracellular germ granules, cytoplasmic RNA-protein condensates that contain a variety of RNAs and proteins essential for germline identity, maintenance, and fertility. P granules are a type of C. elegans germ granule proposed to be sites of mRNA repression. Proper P granule assembly is dependent on PGL-1 and its granule-forming protein relatives. Numerous RNA-binding proteins localize to P granules, like the eIF4E mRNA cap binding homolog, IFE-1. IFE-1 directly interacts with PGL-1 in vivo and in vitro. The molecular function of P granules remains enigmatic. Here, PGL-1 was molecularly dissected in vivo to determine protein regions required for P granule assembly, binding partner recruitment, and germ cell development. A specific region in the PGL-1 C-terminus was necessary and sufficient for IFE-1 recruitment to P granules and for fertility. IFE-1 RNA targets were identified, and reporters of top gene targets were repressed in the adult germline. This repression was dependent on PGL-1 and its IFE-1 binding peptide. These findings provide evidence that IFE-1 and P granules are a factor and site of mRNA repression, respectively. This repression required IFE-1 assembly into P granules, supporting the model that RNA-protein condensate assembly is necessary for its biological and biochemical functions.
    DOI:  https://doi.org/10.1101/2025.09.24.678427
  4. MicroPubl Biol. 2025 ;2025
    C. elegans kinesin 1 regulates meiotic spindle size.
    Rebecca Do, Alma Aquino, Francis McNally.
      During C. elegans female meiosis, kinesin 1 transports yolk granules inward which appears to indirectly drive outward movement of the meiotic spindle to the cortex. Here we examined the size of the centrally located metaphase I meiotic spindle in a germline null allele of kinesin 1 heavy chain. Centrally located meiotic spindles were both longer and wider in kinesin germline null embryos compared with cortical meiotic spindles in controls. Spindle size might be minimized by cortically localized signaling machinery. Alternatively, kinesin 1 which localizes on the spindle during metaphase, may act directly on microtubules to minimize spindle size.
    DOI:  https://doi.org/10.17912/micropub.biology.001820
  5. bioRxiv. 2025 Sep 25. pii: 2025.09.25.678639. [Epub ahead of print]
    The DND1-NANOS3 complex shapes the primordial germ cell transcriptome via a heptanucleotide sequence in mRNA 3' UTRs.
    Masataka Suzawa, Chen Qiu, Ahsan H Polash, Misaki Yamaji, Alexis A Jacob, Wataru Horikawa, Eva M Farroha, Murchana Barua, Xuesong Feng, Chengyu Liu, Jason G Williams, Davide Randazzo, Vittorio Sartorelli, Eugene Valkov, Masashi Yamaji, Traci M Tanaka Hall, Markus Hafner.
      The RNA-binding proteins DND1 and NANOS3 are essential for primordial germ cell survival 1-5 . Their co-immunoprecipitation and overlapping loss-of-function phenotypes suggest joint function 6-8 , yet how they co-regulate target mRNAs remains unclear. Here, we developed Tandem PAR-CLIP and identified a DND1-NANOS3 ribonucleoprotein that specifically recognizes an AUGAAUU heptanucleotide on target mRNAs, termed the NANOS3-dependent DND1 Recognition Element (N3-DRE). mRNAs containing 3'-UTR N3-DREs are aberrantly upregulated in DND1- or NANOS3-deficient germ cells and encode key cell-cycle and epigenome regulators, such as CDK1. Genome editing showed that the N3-DRE is essential for Cdk1 repression in mouse PGCs in vivo . A 1.7-Å crystal structure of the ternary complex of DND1, NANOS3, and CDK1- N3-DRE RNA revealed a continuous RNA-binding surface that confers high-affinity, sequence- specific recognition. Together, these findings define the molecular and functional basis of N3-DRE-mediated mRNA regulation in germ cell development. Moreover, we provide a paradigm of two RNA-binding proteins with low (DND1) or no (NANOS3) intrinsic sequence-specificity, jointly building a high-information-content RNA sequence motif that is different from the sum of their individual preferences. Because RNA-binding protein specificities are typically studied individually 9-13 , rather than in the context of ribonucleoproteins, this type of "two-factor authorization" may be an underappreciated mechanism to protect posttranscriptional gene regulatory networks from aberrant expression of an individual ribonucleoprotein component.
    DOI:  https://doi.org/10.1101/2025.09.25.678639
  6. Reproduction. 2025 Nov 01. pii: e250067. [Epub ahead of print]170(5):
    Centrosomes regulate pronuclear apposition ensuring parental genome unification in cattle.
    Yuki Takada, Shu Hashimoto, Yoshiharu Morimoto.
       In brief: Mammalian zygotes often fail to unify their genomes. This study showed that the position of the centrosome is crucial for regulation of pronuclear apposition and genome unification.
    Abstract: After the sperm enters the ovum, male and female pronuclei carrying the genetic information of both parents are formed. These pronuclei migrate to the center of the ovum, followed by genome unification upon mitosis onset. However, the genomes of some gametes fail to unify. The mechanism by which parental genetic information fails to unify is not yet fully understood. Here, we used immunofluorescence staining and live imaging techniques to study pronuclear migration in fertilized bovine ova. Microtubules play a more important role in pronuclear migration than actin. Centrosomal microtubules regulate the localization of motor dynein bound to the pronuclear membrane. The presence of at least one centrosome between the male and female pronuclei is necessary for apposition of the two pronuclei and genome unification. Our data highlight the importance of centrosome positioning in the apposition of pronuclei and parental genome unification.
    Keywords:  microtubule; pronuclear migration; zygote
    DOI:  https://doi.org/10.1530/REP-25-0067
  7. Commun Biol. 2025 Sep 30. 8(1): 1394
    CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve.
    Xiaoyuan Zhang, Yue Zeng, Zhanzhong Qiao, Kexin Qin, Pei Li, Jiamao Yan, Teng Zhang, Yang Zhou, Junjie Wang, Wei Shen.
      The primordial follicle (PF) pool (also known as ovarian reserve) is the only source of functional eggs during the reproductive lifespan, which formed at embryonic stage in most female mammals and is no longer renewed. CCAAT/enhancer binding protein beta (C/EBPβ) is a transcription factor (TF) and widely expressed in adult ovarian granulosa cells, but its role in the early ovarian development remains unclear. Here, we showed that C/EBPβ was enhanced during PF formation process in mice, and underwent nuclear translocation in germ cells along with the PF assembly (PFA) process. Importantly, the in vitro knockdown of C/EBPβ could inhibit the related proteins expression, resulting in the obstruction of PF formation. Mechanistically, the chromatin accessibility analysis revealed that C/EBPβ binds to the promoter region of the histone acetylase encoding gene Ep300 to promotes its expression, and enhance neurotrophic tyrosine receptor kinase (NTRK) signaling (required for PF formation) by maintaining chromatin accessibility of Furin promoter region. Interestingly, our results verified that the nuclear translocation of C/EBPβ is regulated by its phosphorylation level, and Lamin B1 acts as a "gatekeeper" molecule for the process. In summary, this report suggests that C/EBPβ is a key regulator for the establishment of ovarian reserve in mice.
    DOI:  https://doi.org/10.1038/s42003-025-08798-y
  8. Nat Cell Biol. 2025 Oct 01.
    Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.
    Yanhe Li, Jincan He, Yingdong Liu, Yi Hui, Shanyao Liu, Yalin Zhang, Yan Xiong, Tingting Xu, Ziwen Xu, Zhuoao Zhang, Yan Zhang, Guang Yang, Jia Zhao, Dandan Bai, Xinyi Lei, Xiaochen Kou, Yanhong Zhao, Jing Du, Zheng Guo, Jiqing Yin, Xiaoqing Zhang, Congling Xu, Yawei Gao, Miaoxin Chen, Hong Wang, Cizhong Jiang, Shaorong Gao, Wenqiang Liu.
      Bivalency regulates developmental genes during lineage commitment. However, mechanisms governing bivalent domain establishment, maintenance and resolution in early embryogenesis remain unclear. Here we comprehensively trace bivalent chromatin remodelling throughout mouse peri-implantation development, revealing bifurcated establishment modes that partition epiblast and primitive endoderm regulatory programmes. We identify transiently maintained bivalent domains (TB domains) enriched in the epiblast, where gradual resolution fine-tunes pluripotency progression. Through targeted screening in embryos, we uncover 22 TB domain regulators, including the essential factor ZBTB17. Genetic ablation or degradation of ZBTB17 causes peri-implantation arrest. Mechanistically, ZBTB17 collaborates with KDM6A/B to resolve bivalency by removing H3K27me3 and priming the activation of key pluripotency genes. Remarkably, TB domain dynamics are evolutionarily shared in human pluripotent transitions, with ZBTB17 involvement despite species differences. Our work establishes a framework for bivalent chromatin regulation in early mammalian development and elucidates how its resolution precisely controls lineage commitment.
    DOI:  https://doi.org/10.1038/s41556-025-01776-w
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