bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–12–28
seven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. A 3D in vitro model for studying human implantation and implantation failure.
  2. 3D post-implantation co-culture of human embryo and endometrium.
  3. Modeling human embryo implantation in vitro.
  4. Integrated transcriptomic analysis reveals metabolic remodeling and gene expression networks related to human 8-cell-stage embryo-like cells.
  5. Unsaturated Fatty Acids Are Required for Germline Proliferation and Membrane Structural Integrity in Caenorhabditis elegans.
  6. Conserved RNA helicase Vasa regulates ribonucleoprotein condensates through protein interaction and mRNA recruitment.
  7. Drosophila as a model to study autophagy during oogenesis.
  1. Cell. 2025 Dec 23. pii: S0092-8674(25)01230-9. [Epub ahead of print]
    A 3D in vitro model for studying human implantation and implantation failure.
    Qian Li, Yang Yuan, Wentao Zhao, Yuanjun Li, Juanzi Shi, Yu Xiu, Mi Han, Yan Han, Junmei Zhang, Shuhan Cheng, Xin Qi, Xizhuang Sun, Tan Jia, Jiaqi Xing, Siwei Deng, Xiaodi Yan, Seiya Oura, Hongfei Li, Ying Sun, Huiyao Yuan, Xiaohong Ma, Miaomiao Xin, Jianchao Zhao, Xili Zhu, Cong Wang, Qin Wang, Ge Lin, Xiaokui Yang, Yulei Wei, Jun Wu, Hongmei Wang, Leqian Yu.
      A better understanding of human implantation is essential for improving assisted reproduction outcomes and addressing recurrent implantation failure (RIF). However, ethical constraints and limited access to human embryos make direct studies challenging. To overcome this, we developed a 3D in-chip implantation model using human blastoids or blastocysts co-cultured with a bioengineered human endometrial tissue, termed endometrioid. This system successfully recapitulates key events of human implantation and early post-implantation development. Importantly, when modeling implantation using samples derived from RIF patients, we observed significantly reduced blastoid implantation capability compared with endometrioids from fertile controls. Furthermore, a targeted screen of U.S. Food and Drug Administration (FDA)-approved compounds identified candidates that markedly enhanced implantation efficiency in RIF-derived endometrioids. Together, this 3D platform enables mechanistic investigation of human implantation and implantation failure and offers a scalable approach to evaluate therapeutic strategies for improving embryo-endometrium interaction in a clinical setting.
    Keywords:  endometrioid; human blastoid; human early development; human implantation; recurrent implantation failure; stem cell-derived embryo model
    DOI:  https://doi.org/10.1016/j.cell.2025.10.026
  2. Cell Stem Cell. 2025 Dec 23. pii: S1934-5909(25)00436-9. [Epub ahead of print]
    3D post-implantation co-culture of human embryo and endometrium.
    Jinzhu Song, Rusong Zhao, Yu Zhang, Minghui Lu, Peishu Liu, Tao Li, Cheng Li, Ruijie Yu, Xueyao Chen, Huajian Yang, Xinwen Zhang, Yining Su, Yanli Han, Duanchen Sun, Qingbin Zhou, Zhenzhen Hou, Weijing Liu, Xiaoyuan Gao, Wenrong Tao, Jingye Zhang, Jingwen Wang, Yingying Qin, Hongmei Wang, Keliang Wu, Jun Wu, Zi-Jiang Chen, Han Zhao.
      Embryo-maternal interaction is essential for post-implantation human development. While endometrial organoids have enabled in vitro modeling of the uterine environment, a fully integrated 3D co-culture system with human embryos has not been established. Here, we develop a physiologically relevant 3D platform that supports the co-culture of human embryos with endometrial organoids, enabling reciprocal embryo-maternal communication. This system sustains development to day 14 post-fertilization with structural and molecular fidelity to Carnegie stage landmarks, including yolk sac formation, primordial germ cell specification, and trophoblast maturation. Single-cell transcriptomics and functional assays reveal that the endometrial niche accelerates extravillous trophoblast emergence at day 9 post-fertilization and primes their invasive programs. Disruption of maternal signals, including human chorionic gonadotropin signaling blockade, markedly impairs embryonic progression. This co-culture system provides a powerful and tractable model to dissect human peri- and post-implantation development, with broad relevance to early pregnancy loss, placental biology, and reproductive medicine.
    Keywords:  Carnegie stage; embryo-endometrium interactions; endometrial organoids; extravillous trophoblast; fetal-maternal crosstalk; human blastocysts; human chorionic gonadotropin; human post-implantation development; primordial germ cell; syncytiotrophoblast
    DOI:  https://doi.org/10.1016/j.stem.2025.12.002
  3. Cell. 2025 Dec 23. pii: S0092-8674(25)01232-2. [Epub ahead of print]
    Modeling human embryo implantation in vitro.
    Matteo A Molè, Sarah Elderkin, Irene Zorzan, Christopher Penfold, Nicole Horsley, Alexandra Pokhilko, Max Polanek, Andrea Palomar, Molika Sinha, Yang Wang, Alicia Quiñonero, Charalampos Androulidakis, Richard Acton, Kathryn Balmanno, Anneliese Jarman, Jhanavi Srinivasan, Adam Bendall, Sara Morales-Álvarez, Roberto Yagüe-Serrano, Katie Heywood, Stephen Harbottle, Mina Vasilic, Suzanne Cawood, Srividya Seshadri, Paul Serhal, Lauren Weavers, Ippokratis Sarris, Anastasia Mania, Rachel Gibbons, Lucy Laurier, Immaculada Sánchez-Ribas, Amparo Mercader, Pilar Alamá, Anthony Hoa Bui, Graham J Burton, Tereza Cindrova-Davies, Ridma C Fernando, Afshan McCarthy, Lusine Aghajanova, Liesl Nel-Themaat, Ruth B Lathi, Simon J Cook, Kathy K Niakan, Alexander R Dunn, Francisco Domínguez, Peter J Rugg-Gunn.
      Implantation of a human embryo into the endometrium is a crucial event in gestation, as it marks the initiation of a pregnancy and is prone to high failure rates. We have limited understanding of these stages because of the inaccessibility of implanting embryos and the lack of suitable model systems. Here, we establish an in vitro model that recapitulates the luminal, glandular, and stromal compartments of the superficial layer of receptive human endometrium. Human embryos and blastoids implant into the endometrial model, achieving post-implantation hallmarks including advanced trophoblast structures that underlie early events in placental development. Single-cell RNA sequencing of the embryo-endometrial interface at day 14 uncovers predicted molecular interactions between conceptus and endometrium. Disrupting signaling interactions between extravillous trophoblast and endometrial stromal cells caused defects in trophoblast outgrowth, demonstrating the importance of crosstalk processes to sustain embryogenesis. This platform opens the opportunity to investigate early stages of human embryo implantation.
    Keywords:  development; embryo; embryogenesis; endometrium; human; implantation; in vitro model; placenta; reproduction; trophoblast
    DOI:  https://doi.org/10.1016/j.cell.2025.10.027
  4. Cell Rep. 2025 Dec 19. pii: S2211-1247(25)01520-7. [Epub ahead of print]45(1): 116748
    Integrated transcriptomic analysis reveals metabolic remodeling and gene expression networks related to human 8-cell-stage embryo-like cells.
    Pauliina Paloviita, Sonja Nykänen, Sandra Harjuhaahto, Heli Grym, Reetta Santaniemi, Henna Tyynismaa, Rubén Torregrosa-Muñumer, Sanna Vuoristo.
      Human early development is challenging to study due to limited samples and cell numbers. The emergence of 8-cell-stage (8C) embryo-like cells (8CLCs) offers new opportunities to understand embryonic genome activation (EGA) in humans. Our research compares and characterizes 8CLCs from various stem cell-based systems to determine how well these models reflect human early embryonic development. Using single-cell RNA sequencing datasets from multiple studies, we integrate data to identify key gene co-expression modules, transposable element expression, and biological processes recapitulated in 8CLCs. We identify both mature and intermediate 8CLCs, with the Yoshihara and Mazid datasets best representing 8C embryos. 8CLCs show remodeling in energy and RNA metabolism, regulation of RNA splicing, and ribosome biogenesis, mirroring human 8C embryos. Our findings underscore the importance of distinguishing mature 8CLCs from partially reprogrammed cell states to improve their use as models for human EGA.
    Keywords:  8-cell-stage embryo-like cell; CP: developmental biology; CP: stem cell research; single-cell transcriptomics
    DOI:  https://doi.org/10.1016/j.celrep.2025.116748
  5. Genetics. 2025 Dec 24. pii: iyaf269. [Epub ahead of print]
    Unsaturated Fatty Acids Are Required for Germline Proliferation and Membrane Structural Integrity in Caenorhabditis elegans.
    Bernabe Battista, Laura I Lascarez-Lagunas, Diego de Mendoza, Monica P Colaiácovo.
      Unsaturated fatty acids (UFAs) are critical components of membrane lipids, but their specific roles in germline development and reproductive health remain poorly defined. Here, we investigated the consequences of UFA depletion in the Caenorhabditis elegans germline using an auxin-inducible degron (AID) system to conditionally degrade FAT-7, the major Δ9 stearoyl-CoA desaturase, in a fat-5; fat-6 double mutant background. This strategy bypassed the lethality associated with complete loss of Δ9 desaturase activity, enabling analysis of UFA deficiency in adult animals. UFA depletion led to a dramatic reduction in brood size, elevated embryonic and larval lethality, and a severe loss of germline nuclei. We found that UFAs are essential for mitotic proliferation, DNA replication, and chromosome organization in the germline. Moreover, reduced UFA levels impaired meiotic progression, accompanied by loss of membrane integrity in the syncytial germline. Notably, UFA deficiency altered the spatial distribution and increased the signal intensity of nuclear pore complex (NPC) proteins, suggesting alterations to the nuclear envelope (NE). Together, our findings demonstrate that UFAs are indispensable for germline maintenance, affecting cell cycle progression, chromosome organization, and membrane architecture. These results underscore a fundamental link between acyl chain composition and reproductive success, highlighting the critical role of lipid homeostasis in the germline.
    Keywords:   C. elegans ; AID system; Animalia; fertility; germline; inducible depletion of UFA; meiosis; meiotic progression; membrane structure; mitotic proliferation
    DOI:  https://doi.org/10.1093/genetics/iyaf269
  6. bioRxiv. 2025 Dec 20. pii: 2025.12.19.695503. [Epub ahead of print]
    Conserved RNA helicase Vasa regulates ribonucleoprotein condensates through protein interaction and mRNA recruitment.
    Siran Tian, Hyosik Kim, Harrison A Curnutte, Tatjana Trcek.
      Germlines contain ribonucleoprotein condensates known as germ granules, which concentrate proteins and mRNAs essential for animal development. Vasa, a conserved DEAD-box RNA helicase, is a core and highly concentrated constituent of germ granules. However, its roles within these structures remain poorly understood. Here, we use Drosophila germ granules as a model system to address this question. Applying in vivo and human cell systems, we found that condensation of Oskar (Osk) protein, which nucleates germ granules, occurred independently of Vasa. However, in oocytes lacking detectable Vasa protein, Osk formed aggregated condensates regardless of the eGFP tag. Furthermore, Osk-eGFP showed minimal recovery as measured by fluorescence recovery after photobleaching (FRAP) indicating that its exchange between condensates and their surroundings was greatly reduced in the absence of Vasa. Supporting this result, co-expression of Vasa increased the FRAP recovery of Osk-eGFP condensates and reduced Osk-eGFP partitioning into them in cells. This effect required the interaction between Vasa and Osk, suggesting that by binding Osk, Vasa modulates Osk phase behavior and its condensate material properties. Super-resolution microscopy further revealed that Vasa is required for germ granule mRNA localization to Osk condensates in vivo. Co-expression of Vasa with Osk-eGFP is necessary and sufficient to recruit germ granule mRNAs to condensates in cells. Although this activity depends on Vasa-Osk interaction, the interaction itself is not sufficient. Notably, localization of a conserved germ granule mRNA nanos reduced the FRAP recovery of Osk-eGFP condensates in cells, partially counteracting Vasa effect. Collectively, our findings uncovered a novel function of the DEAD-box RNA helicase Vasa in regulating the material properties of Osk condensates through coordinated protein-protein and protein-mRNA interactions.
    DOI:  https://doi.org/10.64898/2025.12.19.695503
  7. Dev Biol. 2025 Dec 23. pii: S0012-1606(25)00344-6. [Epub ahead of print]
    Drosophila as a model to study autophagy during oogenesis.
    Mrunmayee Kulkarni, Nidhi Murmu, Minal Ayachit, Karan Selarka, Kiran Nilangekar, Bhupendra V Shravage.
      Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular and developmental homeostasis in eukaryotes. Drosophila oogenesis offers a robust model for investigating the spatial and temporal regulation of autophagy within a complex developmental framework that involves cells from both germline and somatic lineages. This tightly regulated cascade of events enables the differentiation of a germline stem cell into a mature oocyte. Autophagy contributes to cellular quality control, nutrient sensing, and the regulation of developmental cell death, all of which are critical for proper egg development and maturation. Disruption of autophagy influences oogenesis, resulting in defective egg chamber development, altered apoptotic dynamics, abnormally shaped mitochondria and compromised mitophagy. Methodological advances, including immunofluorescence-based detection, live imaging using fluorescent reporters, and ultrastructural analysis via transmission electron microscopy, have significantly enhanced the ability to monitor autophagic activity in the ovary. This review summarizes current evidence that establishes autophagy as a key regulatory mechanism during oogenesis. Additionally, it offers an opportunity to investigate the role of autophagy in various cellular processes, including cell division, gene amplification, endocycling, collective cell migration, and cytoplasmic streaming for embryonic polarity, nurse cell dumping, and programmed cell death during Drosophila oogenesis.
    Keywords:  Drosophila; aging; autophagy; cell death; germarium; germline stem cells; mitophagy; nurse cells; oogenesis; starvation; vitellogenesis
    DOI:  https://doi.org/10.1016/j.ydbio.2025.12.013
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