bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–04–20
eleven papers selected by
川一刀
  1. Dppa2 Promotes Early Embryo Development Through Regulating PDH Expression Pattern During Zygotic Genome Activation.
  2. The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1.
  3. Zygotic activation of transposable elements during zebrafish early embryogenesis.
  4. Stem cell-based models of early human development.
  5. Label-free evaluation of mouse embryo quality using time-lapse bright field and optical coherence microscopy.
  6. Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
  7. Cell lineage-resolved embryonic morphological map reveals signaling associated with cell fate and size asymmetry.
  8. Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories.
  9. Progesterone signaling in oviductal epithelial cells modulates the immune response to support preimplantation embryonic development.
  10. Three Novel Mutations in TUBB8 Cause Female Infertility Due to Multiple Morphological Abnormalities of the Oocyte and Early Embryo.
  11. Age-related changes in the cytoplasmic ultrastructure of feline oocytes.
  1. Int J Mol Sci. 2025 Apr 06. pii: 3436. [Epub ahead of print]26(7):
    Dppa2 Promotes Early Embryo Development Through Regulating PDH Expression Pattern During Zygotic Genome Activation.
    Anqi Di, Xinyi Zhang, Lishuang Song, Song Wang, Xuefei Liu, Chunling Bai, Guanghua Su, Guangpeng Li, Lei Yang.
      During embryonic development, zygotic genome activation (ZGA) is a critical event that determines the rational process and the fate of embryonic cells. The tricarboxylic acid cycle (TCA cycle) provides necessary reactants and energy for biological activities such as genome activation, chromatin opening, and epigenetic modifications during ZGA. Recent studies have shown that during ZGA, core enzymes associated with TCA briefly enter the nucleus and participate in initiating the ZGA process. However, the regulatory relationship between ZGA factors, such as Dux, Dppa2, and Dppa4, and the core enzymes of the TCA cycle remains unknown. In this study, we found that Dppa2 plays a key role in ZGA by directly determining the localization of TCA core enzymes, thereby affecting the early embryonic development. To further investigate the effect of Dppa2 on the localization of pyruvate dehydrogenase (PDH), we followed the establishment of an inducible Dppa2 transgenic mouse model. We found that the "chronoectopic" expression of Dppa2 prior to normal ZGA time could lead to the advanced nuclear localization of PDH. In summary, Dppa2 plays a key role in ZGA, directly determining the location of TCA core enzymes in early embryos. This study provides a theoretical basis for early embryonic development at the metabolic regulation level.
    Keywords:  Dppa2; Dppa4; Dux; PDH; TCA; zygotic genome activation
    DOI:  https://doi.org/10.3390/ijms26073436
  2. Nat Struct Mol Biol. 2025 Apr 17.
    The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1.
    Chengpeng Xu, Dandan Qin, Xukun Lu, Qianqian Qi, Yu Wu, Qizhi Wang, Zhuo Han, Xiaoqing Nie, Yongmei Jiang, Dong Deng, Wei Xie, Zheng Gao, Lei Li.
      How cytoplasmic regulators control nuclear events in mammalian oocytes and early embryos remains largely enigmatic. We previously identified a subcortical maternal complex (SCMC) that specifically resides in the cytoplasm of mammalian oocytes and early embryos but is also involved in nuclear events. Nevertheless, how the cytoplasmic SCMC exerts its role in nuclear processes remains unknown. In this study, we unveil SPIN1, a histone methylation reader, as a novel member of the SCMC. The SCMC component FILIA tightly regulates the expression and cytoplasmic localization of SPIN1 through direct interaction. When the expression of FILIA is decreased because of genetic mutations of SCMC genes, SPIN1 expression is dramatically reduced but the residual SPIN1 translocates into the nucleus. The abnormal nuclear presence of SPIN1 impairs H3K4me3 reprogramming, zygotic genome activation and physiological embryonic development. Inhibiting the interaction between SPIN1 and H3K4me3 partially rescues the abnormal phenotype in FILIA-null embryos. Mechanistically, SPIN1 partially perturbs the demethylation process by competing with KDM5B for binding to H3K4me3. Collectively, our work highlights the complexity of the mammalian SCMC and oocyte-to-embryo transition, revealing an intricate regulatory mechanism that facilitates the smooth progression of this process.
    DOI:  https://doi.org/10.1038/s41594-025-01538-0
  3. Nat Commun. 2025 Apr 18. 16(1): 3692
    Zygotic activation of transposable elements during zebrafish early embryogenesis.
    Bo Li, Ting Li, Dingjie Wang, Ying Yang, Puwen Tan, Yunhao Wang, Yun-Gui Yang, Shunji Jia, Kin Fai Au.
      Although previous studies have shown that transposable elements (TEs) are conservatively activated to play key roles during early embryonic development, the details of zygotic TE activation (ZTA) remain poorly understood. Here, we employ long-read sequencing to precisely identify that only a small subset of TE loci are activated among numerous copies, allowing us to map their hierarchical transcriptional cascades at the single-locus and single-transcript level. Despite the heterogeneity of ZTA across family, subfamily, locus, and transcript levels, our findings reveal that ZTA follows a markedly different pattern from conventional zygotic gene activation (ZGA): ZTA occurs significantly later than ZGA and shows a pronounced bias for nuclear localization of TE transcripts. This study advances our understanding of TE activation by providing a high-resolution view of TE copies and creating a comprehensive catalog of thousands of previously unannotated transcripts and genes that are activated during early zebrafish embryogenesis. Among these genes, we highlight two that are essential for zebrafish development.
    DOI:  https://doi.org/10.1038/s41467-025-58863-7
  4. Development. 2025 Apr 15. pii: dev204543. [Epub ahead of print]152(8):
    Stem cell-based models of early human development.
    Lizhong Liu, Jun Wu.
      Stem cell-based embryo models (SCBEMs) are structures generated from three-dimensional (3D) culture of pluripotent stem cells and their derivatives, utilizing mechanical and/or chemical cues to facilitate lineage differentiation, self-organization and morphogenesis. These models partially mimic early embryos, which would otherwise be difficult to access. SCBEMs have been established in mice, livestock, nonhuman primates and humans. Here, we focus on recently developed human models, with an emphasis on the peri-implantation stage and the aspects of human development these SCBEMs recapitulate.
    Keywords:  Gastrulation; Human pluripotent stem cells; Implantation; Stem cell-based embryo models
    DOI:  https://doi.org/10.1242/dev.204543
  5. Commun Biol. 2025 Apr 15. 8(1): 612
    Label-free evaluation of mouse embryo quality using time-lapse bright field and optical coherence microscopy.
    Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou.
      The selection of high-quality embryos is essential to enhance the implantation rate for in vitro fertilization (IVF). Optical coherence microscopy (OCM) can noninvasively provide three-dimensional (3D) high-resolution imaging of developing embryos. The revealed microstructures can be used for accurate embryo evaluation. Here, we acquire time-lapse 3D OCM images with co-registered bright-field imaging on mouse embryo development from the one-cell stage to the fully hatched blastocyst inside an incubator. Our results demonstrate the capability of OCM to detect structural features of the developing embryos. The second and third embryonic cell cycles are indicated to be associated with blastocyst formation and the hatching capability. OCM-based time-lapse technology holds the potential to enrich early embryo development insights and streamline embryo selection within IVF clinics.
    DOI:  https://doi.org/10.1038/s42003-025-08044-5
  6. bioRxiv. 2025 Apr 03. pii: 2025.04.02.646881. [Epub ahead of print]
    Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
    Gisela Cairo, Olha Kholod, Olivia Palmer, Brittany A Goods, Soni Lacefield.
      Mammalian female meiosis is tightly regulated to produce a developmentally competent egg. Oocytes enter meiosis in the fetal ovary and then arrest at prophase I until sexual maturation. Upon hormonal stimulation, a subset of oocytes resumes meiosis at which time, new transcription is halted. Oocytes then complete meiosis I, enter metaphase II, and arrest until fertilization, a process essential for egg competency and fertility. The MOS kinase is a key regulator of the metaphase II arrest, activating the MAPK signaling cascade. Loss of MOS in female mice disrupts the maintenance of the metaphase II arrest, leading some eggs to extrude two polar bodies and some to divide beyond anaphase II. To investigate the consequences of the Mos deletion, we performed live imaging and found that mos -/- eggs exhibit transient chromosome separation events in meiosis I, suggesting a role for MOS in coordinating the timing of meiotic divisions. Further analysis showed that new transcription is required for mos -/- eggs to undergo additional divisions but not for second polar body extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wildtype and mos -/- eggs, including those with only one polar body. Many of the differentially expressed genes were involved in cell cycle regulation, including Aurka , Bub3 , and Cdk7 . Other upregulated pathways included metabolism of RNA, transcription, and neddylation. Furthermore, the gene expression profile of mos -/- eggs was markedly different from that of wildtype eggs chemically activated to undergo embryo-like divisions. Our findings demonstrate that MOS plays a crucial role in meiotic cell cycle regulation and helps ensure that the egg maintains the proper transcriptome necessary for developmental competence.
    DOI:  https://doi.org/10.1101/2025.04.02.646881
  7. Nat Commun. 2025 Apr 18. 16(1): 3700
    Cell lineage-resolved embryonic morphological map reveals signaling associated with cell fate and size asymmetry.
    Guoye Guan, Zelin Li, Yiming Ma, Pohao Ye, Jianfeng Cao, Ming-Kin Wong, Vincy Wing Sze Ho, Lu-Yan Chan, Hong Yan, Chao Tang, Zhongying Zhao.
      How cells change shape is crucial for the development of tissues, organs and embryos. However, studying these shape changes in detail is challenging. Here we present a comprehensive real-time cellular map that covers over 95% of the cells formed during Caenorhabditis elegans embryogenesis, featuring nearly 400,000 3D cell regions. This map includes information on each cell's identity, lineage, fate, shape, volume, surface area, contact area, and gene expression profiles, all accessible through our user-friendly software and website. Our map allows for detailed analysis of key developmental processes, including dorsal intercalation, intestinal formation, and muscle assembly. We show how Notch and Wnt signaling pathways, along with mechanical forces from cell interactions, regulate cell fate decisions and size asymmetries. Our findings suggest that repeated Notch signaling drives size disparities in the large excretory cell, which functions like a kidney. This work sets the stage for in-depth studies of the mechanisms controlling cell fate differentiation and morphogenesis.
    DOI:  https://doi.org/10.1038/s41467-025-58878-0
  8. Nat Commun. 2025 Apr 17. 16(1): 3658
    Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories.
    Klaudija Daugelaite, Perrine Lacour, Ivana Winkler, Marie-Luise Koch, Anja Schneider, Nina Schneider, Francesca Coraggio, Alexander Tolkachov, Xuan Phuoc Nguyen, Adriana Vilkaite, Julia Rehnitz, Duncan T Odom, Angela Goncalves.
      In vitro fertilization efficiency is limited in part because a fraction of retrieved oocytes fails to fertilize. Accurately evaluating their quality could significantly improve in vitro fertilization efficiency, which would require better understanding how their maturation may be disrupted. Here, we quantitatively investigate the interplay between superovulation and aging in mouse oocytes and their paired granulosa cells using a newly adapted experimental methodology. We test the hypothesis that superovulation disrupts oocyte maturation, revealing the key intercellular communication pathways dysregulated at the transcriptional level by forced hormonal stimulation. We further demonstrate that granulosa cell transcriptional markers can prospectively predict an associated oocyte's early developmental potential. By using naturally ovulated old mice as a non-stimulated reference, we show that aging and superovulation dysregulate similar genes and interact with each other. By comparing mice and human transcriptional responses of granulosa cells, we find that age-related dysregulation of hormonal responses and cell cycle pathways are shared, though substantial divergence exists in other pathways.
    DOI:  https://doi.org/10.1038/s41467-025-58451-9
  9. Sci Adv. 2025 Apr 18. 11(16): eadt6113
    Progesterone signaling in oviductal epithelial cells modulates the immune response to support preimplantation embryonic development.
    Emily A McGlade, Jiude Mao, Kalli K Stephens, Ryan M Marquardt, Feyza Nur Arguc, Peter F Lais, San-Pin Wu, Sarayut Winuthayanon, Haval Shirwan, Esma S Yolcu, Mark I Hunter, James K Pru, John P Lydon, Francesco J DeMayo, Wipawee Winuthayanon.
      More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs significantly reduced IL-22 levels in the oviducts and rescued embryonic developmental rates in Pgrd/d females. Coculture of wild-type zygotes with IL-22 significantly decreased the number of expanded blastocysts. Our findings suggest that progesterone signaling is vital for immunoregulation and normal preimplantation development, potentially providing insights for developing diagnostic tools and therapeutic strategies to address pregnancy failures.
    DOI:  https://doi.org/10.1126/sciadv.adt6113
  10. Reprod Sci. 2025 Apr 17.
    Three Novel Mutations in TUBB8 Cause Female Infertility Due to Multiple Morphological Abnormalities of the Oocyte and Early Embryo.
    Duan Li, Guanghui Yuan, Xiaoxiao Wang, Jiao Zhuang, Lie Wang, Yingxue Liu, Xiaowen Liu, Linfang Han, Huaiqian Dou, Bing Li, Cuifang Hao.
      Recent years have seen a global increase in infertility, affecting up to 17.5% of the population. For successful human reproduction, the proper development process of the oocyte, fertilization, and early embryo is required. Assisted reproductive technology (ART), which is the primary treatment for infertility, uses the morphology of oocytes and zygotes as parameters to predict ART outcomes. However, factors such as large perivitelline space (PVS), centrally located granular cytoplasm (CLGC), multi-pronuclei (MPN) formation, and final early embryonic development arrest often lead to repeated failure of ART treatment. Genetic analysis has identified various pathogenic genetic factors contributing to infertility, suggesting that genetic variation plays a significant role in recurrent ART treatment failure. However, maternal genes responsible for large PVS, CLGC, and MPN formation are rarely reported. In this study involving Whole Exome Sequencing (WES) and Sanger sequencing validation, three novel heterozygous missense mutations (p.M403V, p.R306H, p.H190Y) in TUBB8 were identified as being associated with large PVS, CLGC, MPN formation, and early embryonic development arrest. These mutant sites are evolutionarily conserved in different species. Additionally, in silico and in vitro experiments demonstrate that these variants disrupt the conformation, expression, and microtubule structures of the TUBB8 protein. Therefore, these findings contribute significantly to understanding TUBB8-related large PVS, CLGC, and MPN formation in the context of ARTs. This broadens our insight into the genetic connection in human reproduction and emphasizes the importance of comprehensive genetic screening and personalized intervention strategies for PVS, CLGC, and MPN formation.
    Keywords:  Assisted reproductive technology; Early embryonic development; Female infertility; Oocyte morphology; TUBB8
    DOI:  https://doi.org/10.1007/s43032-025-01844-4
  11. Sci Rep. 2025 Apr 12. 15(1): 12668
    Age-related changes in the cytoplasmic ultrastructure of feline oocytes.
    Brągiel Natalia, Perrin John, Młodawska Wiesława, Niżański Wojciech, Podhorska-Okołów Marzenna, Haczkiewicz-Leśniak Katarzyna, Kulus Michał, Ochota Małgorzata.
      This study elucidates the impact of aging on the cellular architecture of feline oocytes, with a particular emphasis on organelles essential for fertilization and embryo development. Using transmission electron microscopy (TEM), the research compares oocytes from prepubescent, cycling adult, and aged cats, revealing notable differences in the arrangement of key structures, particularly mitochondria, lipid droplets, and vacuoles. Oocytes from adult donors are at their metabolic peak, demonstrating a higher concentration of mitochondria near lipid droplets, supporting efficient energy metabolism. In contrast, younger and older oocytes exhibit larger lipid droplets and reduced mitochondrial density, indicative of diminished metabolic activity. These findings not only underscore the necessity of selecting an optimal donor age for in vitro fertilization but also suggest potential biomarkers for oocyte quality assessment. This novel insight offers promising strategies to enhance reproductive success, improve assisted reproduction outcomes, and support feline conservation efforts.
    Keywords:  Aging; Cats; Electron microscopy; Fertility; Oocytes; Reproductive biology
    DOI:  https://doi.org/10.1038/s41598-025-96983-8
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