bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–03–30
six papers selected by
川一刀
  1. EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development.
  2. Chromatin landscape at cis-regulatory elements orchestrates cell fate decisions in early embryogenesis.
  3. Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2.
  4. Absence of CDK12 in oocyte leads to female infertility.
  5. The emergence of human primordial germ cell-like cells in stem cell-derived gastruloids.
  6. Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species.
  1. Theriogenology. 2025 Mar 22. pii: S0093-691X(25)00124-4. [Epub ahead of print]240 117398
    EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development.
    Zengyou Ma, Yanyan Zhang, Xueqi Tian, Wenjie Lu, Hui Peng.
      The protein translation process is an important part of mammalian ovogenesis and early embryonic development. The eukaryotic translation initiation factors 4E family (eIF4E) initiates the eukaryotic mRNA translation process and plays an important role in protein synthesis. The aim of this research was to analyze the expression and localization of eIF4E family members and the role of EIF4E1B in mouse oocyte maturation and early embryonic development. Here, we report the expression and localization of EIF4E1, EIF4E2, and EIF4E3 in multiple tissues, during oocyte maturation and early embryonic development in mice. However, EIF4E1B was expressed only in ovarian and testicular tissues, and this protein was detected only at the one-to two-cell embryonic stage of early embryos. Moreover, knockdown of eIF4E1b in GV-stage oocytes and zygotes resulted in significant reductions in the rates of oocyte maturation and blastocyst formation, respectively. Further investigation revealed that EIF4E1B interacted with the PPP2CA and HSPA1A proteins and might be involved in the mouse oocyte maturation process. These results provide the first evidence for a novel function of EIF4E1B in oocyte maturation and early embryonic development in mice.
    Keywords:  Developmental arrest; EIF4E1B; Early embryos; Mice; Oocyte maturation
    DOI:  https://doi.org/10.1016/j.theriogenology.2025.117398
  2. Nat Commun. 2025 Mar 27. 16(1): 3007
    Chromatin landscape at cis-regulatory elements orchestrates cell fate decisions in early embryogenesis.
    Francesco Cardamone, Annamaria Piva, Eva Löser, Bastian Eichenberger, Mari Carmen Romero-Mulero, Fides Zenk, Emily J Shields, Nina Cabezas-Wallscheid, Roberto Bonasio, Guido Tiana, Yinxiu Zhan, Nicola Iovino.
      The establishment of germ layers during early development is crucial for body formation. The Drosophila zygote serves as a model for investigating these transitions in relation to the chromatin landscape. However, the cellular heterogeneity of the blastoderm embryo poses a challenge for gaining mechanistic insights. Using 10× Multiome, we simultaneously analyzed the in vivo epigenomic and transcriptomic states of wild-type, E(z)-, and CBP-depleted embryos during zygotic genome activation at single-cell resolution. We found that pre-zygotic H3K27me3 safeguards tissue-specific gene expression by modulating cis-regulatory elements. Furthermore, we demonstrate that CBP is essential for cell fate specification functioning as a transcriptional activator by stabilizing transcriptional factors binding at key developmental genes. Surprisingly, while CBP depletion leads to transcriptional arrest, chromatin accessibility continues to progress independently through the retention of stalled RNA Polymerase II. Our study reveals fundamental principles of chromatin-mediated gene regulation essential for establishing and maintaining cellular identities during early embryogenesis.
    DOI:  https://doi.org/10.1038/s41467-025-57719-4
  3. Science. 2025 Mar 28. 387(6741): eadp4319
    Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2.
    Mengyao Li, Zhenhuan Jiang, Xueqiang Xu, Xinglong Wu, Yun Liu, Kexuan Chen, Yuhan Liao, Wen Li, Xiao Wang, Yuqing Guo, Bo Zhang, Lu Wen, Kehkooi Kee, Fuchou Tang.
      In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. Here, we developed scNanoATAC-seq2, a single-cell assay for transposase-accessible chromatin using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and two-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in noncanonical imprinting, imprinted X chromosome inactivation, and low-mappability genomic regions, such as repetitive elements and paralogs. Our data provide insights into chromatin dynamics during mammalian preimplantation development and lineage differentiation.
    DOI:  https://doi.org/10.1126/science.adp4319
  4. Cell Death Dis. 2025 Mar 27. 16(1): 213
    Absence of CDK12 in oocyte leads to female infertility.
    Denisa Jansova, Veronika Sedmikova, Fatima J Berro, Daria Aleshkina, Michal Dvoran, Michal Kubelka, Jitka Rezacova, Jana Rutarova, Jiri Kohoutek, Andrej Susor.
      Transcriptional activity and gene expression are critical for the development of mature, meiotically competent oocytes. Our study demonstrates that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as fully developed oocytes capable of completing meiosis I are absent from the ovaries. Mechanistically, CDK12 regulates RNA polymerase II activity in growing oocytes and ensures the maintenance of the physiological maternal transcriptome, which is essential for protein synthesis that drives further oocyte growth. Notably, CDK12-deficient growing oocytes exhibit a 71% reduction in transcriptional activity. Furthermore, impaired oocyte development disrupts folliculogenesis, leading to premature ovarian failure without terminal follicle maturation or ovulation. In conclusion, our findings identify CDK12 as a key master regulator of the oocyte transcriptional program and gene expression, indispensable for oocyte growth and female fertility. A schematic illustrating the effects of loss of CDK12 in mammalian oocytes on the regulation of transcription by polymerase II and the concomitant effects on translation. This disruption leads to an aberrant transcriptome and translatome, resulting in the absence of fully mature oocytes and ultimately female sterility.
    DOI:  https://doi.org/10.1038/s41419-025-07536-w
  5. Sci Adv. 2025 Mar 28. 11(13): eado1350
    The emergence of human primordial germ cell-like cells in stem cell-derived gastruloids.
    Jitesh Neupane, Gabriele Lubatti, Theresa Gross-Thebing, Mayra Luisa Ruiz Tejada Segura, Richard Butler, Sargon Gross-Thebing, Sabine Dietmann, Antonio Scialdone, M Azim Surani.
      Most advances in early human postimplantation development depend on animal studies and stem cell-based embryo models. Here, we present self-organized three-dimensional human gastruloids (hGs) derived from embryonic stem cells. The transcriptome profile of day 3 hGs aligned with Carnegie stage 7 human gastrula, with cell types and differentiation trajectories consistent with human gastrulation. Notably, we observed the emergence of nascent primordial germ cell-like cells (PGCLCs), but without exogenous bone morphogenetic protein (BMP) signaling, which is essential for the PGCLC fate. A mutation in the ISL1 gene affects amnion-like cells and leads to a loss of PGCLCs; the addition of exogenous BMP2 rescues the PGCLC fate, indicating that the amnion may provide endogenous BMP signaling. Our model of early human embryogenesis will enable further exploration of the germ line and other early human lineages.
    DOI:  https://doi.org/10.1126/sciadv.ado1350
  6. Biol Reprod. 2025 Mar 23. pii: ioaf059. [Epub ahead of print]
    Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species.
    Hana Kubo, Christopher J McCauley, Mary B Zelinski, Monica M Laronda.
      Folliculogenesis encompasses many stages as the somatic granulosa and theca cells support oocytes through growth and maturation. A novel follicle stage, between primordial and transitional stages, was identified in mice and defined as "zip". Like all other follicle stages, the "zip" stage is characterized by its granulosa cell morphology. The "wedge" GC morphology in zip follicles is predicted to be the first granulosa cell division, marking the transition from squamous to cuboidal morphology. Here, zip and transitional stages were identified in histological sections of porcine, bovine, rhesus monkey, and human ovaries. Several growth dynamics characterized at these follicle stages were conserved between species. Oocyte diameter and area increased between the primordial and transitional stages in the porcine ovary and between the primordial and primary stages in the rhesus monkey ovary but appeared unchanged in bovine and human ovaries. In all species except for pigs, granulosa cell number and height increased at stages earlier than observed changes in the oocyte. Furthermore, there were differences in the percentage of zip and transitional follicle stages present in the cortical region across species. This implies that there may be species-dependent activation and growth mechanisms that require further study. The parameters defined here for identifying and characterizing the zip and transitional follicle stages across species can act as a tool for measuring factors that perturb or induce primordial follicle activation or effect follicle morphometric parameters in support of future innovations for fertility preservation and restoration.
    Keywords:  Folliculogenesis; Mammalian reproduction; Oocyte; Ovary; Reproduction
    DOI:  https://doi.org/10.1093/biolre/ioaf059
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