bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–03–02
fourteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Hallmarks of ovarian aging.
  2. Genome-coverage single-cell histone modifications for embryo lineage tracing.
  3. Mammalian oocytes receive maternal-effect RNAs from granulosa cells.
  4. Maternal PRDM10 activates essential genes for oocyte-to-embryo transition.
  5. The synaptonemal complex aligns meiotic chromosomes by wetting.
  6. Centrosome-assisted assembly of the Balbiani body.
  7. Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?
  8. Emerging cooperativity between Oct4 and Sox2 governs the pluripotency network in early mouse embryos.
  9. The transcription factor SRF regulates MERVL retrotransposons and gene expression during zygotic genome activation.
  10. Decoding the Molecular Landscape of Prepubertal Oocyte Maturation: GTPBP4 as a Key Driver of In Vitro Developmental Competence.
  11. Suppression of FOXO3 by BMP signaling contribute to the different primordial germ cell proliferation between layers and broilers.
  12. Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos.
  13. The Mammalian Oocyte: A Central Hub for Cellular Reprogramming and Stemness.
  14. Mitochondria as Indispensable Yet Replaceable Components of Germ Plasm: Insights into PGCs Specification in Sturgeons.
  1. Trends Endocrinol Metab. 2025 Feb 24. pii: S1043-2760(25)00018-9. [Epub ahead of print]
    Hallmarks of ovarian aging.
    Chuqing Wu, Dan Chen, Michael B Stout, Meng Wu, Shixuan Wang.
      Ovarian aging is considered to be the pacemaker of female aging, and is linked to various comorbidities such as osteoporosis, cardiovascular diseases, and cognitive decline. Many efforts have been made to determine the mechanisms underlying ovarian aging, but their potential to act as hallmarks to predict and intervene in this process currently remains unclear. In this review we propose nine hallmarks as common features of ovarian aging: genomic instability, telomere attrition, epigenetic alterations, impaired autophagy, cellular senescence, deregulated nutrient-sensing, mitochondrial dysfunction, oxidative stress, and chronic inflammation. Understanding the interaction between these hallmarks poses a significant challenge but may also pave the way to the identification of pharmaceutical targets that can attenuate ovarian aging.
    Keywords:  endocrine; fertility; hallmarks; oocyte; ovarian aging
    DOI:  https://doi.org/10.1016/j.tem.2025.01.005
  2. Nature. 2025 Feb 26.
    Genome-coverage single-cell histone modifications for embryo lineage tracing.
    Min Liu, Yanzhu Yue, Xubin Chen, Kexin Xian, Chao Dong, Ming Shi, Haiqing Xiong, Kang Tian, Yuzhe Li, Qiangfeng Cliff Zhang, Aibin He.
      Substantial epigenetic resetting during early embryo development from fertilization to blastocyst formation ensures zygotic genome activation and leads to progressive cellular heterogeneities1-3. Mapping single-cell epigenomic profiles of core histone modifications that cover each individual cell is a fundamental goal in developmental biology. Here we develop target chromatin indexing and tagmentation (TACIT), a method that enabled genome-coverage single-cell profiling of seven histone modifications across mouse early embryos. We integrated these single-cell histone modifications with single-cell RNA sequencing data to chart a single-cell resolution epigenetic landscape. Multimodal chromatin-state annotations showed that the onset of zygotic genome activation at the early two-cell stage already primes heterogeneities in totipotency. We used machine learning to identify totipotency gene regulatory networks, including stage-specific transposable elements and putative transcription factors. CRISPR activation of a combination of these identified transcription factors induced totipotency activation in mouse embryonic stem cells. Together with single-cell co-profiles of multiple histone modifications, we developed a model that predicts the earliest cell branching towards the inner cell mass and the trophectoderm in latent multimodal space and identifies regulatory elements and previously unknown lineage-specifying transcription factors. Our work provides insights into single-cell epigenetic reprogramming, multimodal regulation of cellular lineages and cell-fate priming during mouse pre-implantation development.
    DOI:  https://doi.org/10.1038/s41586-025-08656-1
  3. bioRxiv. 2025 Feb 11. pii: 2025.02.10.637575. [Epub ahead of print]
    Mammalian oocytes receive maternal-effect RNAs from granulosa cells.
    Caroline A Doherty, Abdulfatai Tijjani, Steven C Munger, Diana J Laird.
      It is currently thought that growing mammalian oocytes receive only small molecules via gap junctions from surrounding support cells, the granulosa cells. From the study of chimeric preantral oocyte and granulosa cell reaggregations, we provide evidence that growing mouse oocytes receive mRNAs from granulosa cells. Among the >1,000 granulosa-transcribed RNAs we identified in the oocyte, those that contribute to proper oocyte maturation and early embryo development were highly enriched. Predicted motifs for two RNA-binding proteins that function in RNA trafficking, FMRP and TDP43, were abundant in the UTRs of the granulosa-derived transcripts. Immunostaining demonstrated that both FMRP and TDP43 co-localize with the actin-rich granulosa cell protrusions that span the zone pellucida and connect to the oocyte, suggesting their role in importing mRNAs. Our results offer the possibility that oocyte failure may not always reflect an intrinsic oocyte deficiency but could arise from insufficient supply of maternal transcripts by granulosa cells during oocyte growth.
    DOI:  https://doi.org/10.1101/2025.02.10.637575
  4. Nat Commun. 2025 Feb 24. 16(1): 1939
    Maternal PRDM10 activates essential genes for oocyte-to-embryo transition.
    Michelle K Y Seah, Brenda Y Han, Yan Huang, Louise J H Rasmussen, Andrina J Stäubli, Judith Bello-Rodríguez, Andrew Chi-Ho Chan, Maxime Gasnier, Heike Wollmann, Ernesto Guccione, Daniel M Messerschmidt.
      PR/SET domain-containing (PRDM) proteins are metazoan-specific transcriptional regulators that play diverse roles in mammalian development and disease. Several members such as PRDM1, PRDM14 and PRDM9, have been implicated in germ cell specification and homoeostasis and are essential to fertility-related processes. Others, such as PRDM14, PRDM15 and PRDM10 play a role in early embryogenesis and embryonic stem cell maintenance. Here, we describe the first PRDM family member with a maternal effect. Absence of maternal Prdm10 results in catastrophic failure of oocyte-to-embryo transition and complete arrest at the 2-cell stage. We describe multiple defects in oocytes, zygotes and 2-cell stage embryos relating to the failure to accumulate PRDM10 target gene transcripts in the egg. Transcriptomic analysis and integration of genome-wide chromatin-binding data reveals new and essential PRDM10 targets, including the cytoskeletal protein encoding gene Septin11. We demonstrate that the failure to express maternal Septin11, in the absence of maternal PRDM10, disrupts Septin-complex assembly at the polar body extrusion site in MII oocytes. Our study sheds light into the essentiality of maternal PRDM10, the requirement of the maternal Septin-complex and the likely evolutionary conservation of this regulatory axis in human female germ cells.
    DOI:  https://doi.org/10.1038/s41467-025-56991-8
  5. Sci Adv. 2025 Feb 28. 11(9): eadt5675
    The synaptonemal complex aligns meiotic chromosomes by wetting.
    Spencer G Gordon, Alyssa A Rodriguez, Yajie Gu, Kevin D Corbett, Chiu Fan Lee, Ofer Rog.
      During meiosis, the parental chromosomes are drawn together to enable exchange of genetic information. Chromosomes are aligned through the assembly of a conserved interface, the synaptonemal complex, composed of a central region that forms between two parallel chromosomal backbones called axes. Here, we identify the axis-central region interface in C. elegans, containing a conserved positive patch on the axis component HIM-3 and the negative C terminus of the central region protein SYP-5. Crucially, the canonical ultrastructure of the synaptonemal complex is altered upon weakening this interface using charge-reversal mutations. We developed a thermodynamic model that recapitulates our experimental observations, indicating that the liquid-like central region can assemble by wetting the axes without active energy consumption. More broadly, our data show that condensation drives tightly regulated nuclear reorganization during sexual reproduction.
    DOI:  https://doi.org/10.1126/sciadv.adt5675
  6. bioRxiv. 2025 Feb 12. pii: 2025.02.11.637656. [Epub ahead of print]
    Centrosome-assisted assembly of the Balbiani body.
    Divyanshi
      The Balbiani body (Bb), which was discovered about 170 years ago, is a membraneless organelle in the oocyte in most species. In organisms like Xenopus and Zebrafish, Bb accumulates mitochondria, endoplasmic reticulum (ER), and germline determinants and regulates the proper localization of germline determinants. The Bb forms around the centrosome in the oocyte during early oogenesis. The mechanism behind its assembly has gained attention only very recently. Here, we report that overexpression of the germ plasm matrix protein Xvelo leads to the formation of a 'Bb-like' structure in somatic cells. The 'Bb-like' structure assembles around the centrosome and selectively recruits mitochondria, ER, and germline determinants. Taking advantage of this system, we investigated the roles of centrosome components on the assembly of Xvelo. Our results reveal that multiple components of the centrosome, including Sas6, Cenexin, and DZIP1, interact with Xvelo and promote its assembly, with Sas6 exhibiting the most prominent activity. Importantly, knocking down Sas6, Cenexin, and DZIP1 individually or in combination resulted in reduced Xvelo aggregates. Taken together, our work suggests that the centrosome may function as a nucleation center to promote the initiation of Xvelo assembly, resulting in the formation of the Bb around the centrosome.
    DOI:  https://doi.org/10.1101/2025.02.11.637656
  7. Hum Reprod. 2025 Feb 22. pii: deaf024. [Epub ahead of print]
    Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?
    Murat Erden, Kutluk H Oktay.
      Despite significant advances in fertility preservation, no proven pharmacological options exist to protect ovarian primordial follicle reserve from chemotherapy-induced damage. Developing targeted gonadoprotective treatments will require an improved understanding of the molecular mechanisms underlying chemotherapy-induced primordial follicle depletion. While there is robust evidence that gonadotoxic chemotherapy induces primordial follicle death by causing DNA double-strand breaks which trigger apoptotic death, follicle activation leading to 'burn-out' of the ovarian reserve has been suggested as an alternative mechanism. Here, we critically evaluated whether primordial follicle activation is a significant mechanism of chemotherapy-induced ovarian reserve depletion in humans. We assessed the causal relationship between chemotherapy exposure and primordial follicle activation by applying the Bradford Hill criteria.
    Keywords:  chemotherapy; cyclophosphamide; fertility preservation; ovarian damage; ovarian reserve; primordial follicle
    DOI:  https://doi.org/10.1093/humrep/deaf024
  8. Elife. 2025 Feb 27. pii: RP100735. [Epub ahead of print]13
    Emerging cooperativity between Oct4 and Sox2 governs the pluripotency network in early mouse embryos.
    Yanlin Hou, Zhengwen Nie, Qi Jiang, Sergiy Velychko, Sandra Heising, Ivan Bedzhov, Guangming Wu, Kenjiro Adachi, Hans R Scholer.
      During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
    Keywords:  Oct4; Sox2; chromatin accessibility; developmental biology; embryonic development; inner cell mass; mouse; transcriptome
    DOI:  https://doi.org/10.7554/eLife.100735
  9. Genes Dev. 2025 Feb 27.
    The transcription factor SRF regulates MERVL retrotransposons and gene expression during zygotic genome activation.
    Clara Hermant, Carlos Michel Mourra-Díaz, Marlies E Oomen, Luis Altamirano-Pacheco, Mrinmoy Pal, Tsunetoshi Nakatani, Maria-Elena Torres-Padilla.
      The regulatory circuitry of cell-specific transcriptional programs is thought to be influenced by transposable elements (TEs), whereby TEs serve as raw material for the diversification and genome-wide distribution of genetic elements that contain cis-regulatory activity. However, the transcriptional activators of TEs in relevant physiological contexts are largely unknown. Here, we undertook an evolutionary approach to identify regulators of two main families of MERVL, a major regulator of transcription during early mouse development. Using a combination of phyloregulatory, transcriptomic, and loss-of-function approaches, we demonstrate that SRF is a novel regulator of MERVL and embryonic transcription during zygotic genome activation. By resolving the phylogenetic history of two major MERVL families, we delineate the evolutionary acquisition of SRF and DUX binding sites and show that the acquisition of the SRF site precedes that of DUX. SRF contributes to embryonic transcription through the regulation of MERVLs, which in turn serve as promoters for host genes. Our work identifies new transcriptional regulators and TEs that shape the gene expression programs in early embryos and highlights the process of TE domestication via the sequential acquisition of transcription factor binding sites and coevolution with the host.
    Keywords:  MERVL; mouse embryos; retrotransposons; transcription
    DOI:  https://doi.org/10.1101/gad.352270.124
  10. Cell Prolif. 2025 Feb 28. e70017
    Decoding the Molecular Landscape of Prepubertal Oocyte Maturation: GTPBP4 as a Key Driver of In Vitro Developmental Competence.
    Jianpeng Qin, Yaozong Wei, Ao Ning, Wenqi Hu, Pengcheng Wan, Beijia Cao, Bo Pan, Tianyi Lv, Kunlin Du, Xueling Yao, Shuqi Zou, Xiangyi Chen, Shengqin Zang, Jiangfeng Ye, Guozhi Yu, Qiuxia Liang, Liuhong Shen, Lin Zhang, Xiang Chen, Keren Cheng, Li Meng, Guangbin Zhou.
      The intricate mechanisms driving oocyte maturation remain only partially understood, especially within the domains of domestic animal reproduction and translational medicine. In the case of prepubertal girls, the clinical challenge is especially pronounced, as ovarian tissue cryopreservation-though promising-remains an experimental technique necessitating rigorous scientific validation to guarantee the developmental potential of preserved materials and facilitate broader clinical adoption. To address these knowledge gaps, while considering the ethical implications, we applied transcriptome and translatome sequencing to comprehensively profile the transcriptional and translational dynamics of oocyte maturation in adult and prepubertal goats. Our analyses uncovered a sequential transition in gene expression regulation, shifting from cytoplasmic processes to chromosome segregation during the maturation process. Comparative profiling between adult and prepubertal goat oocytes revealed critical regulatory factors essential for prepubertal oocyte maturation. These include genes involved in organelle function (GTPBP4 and TOMM7), spindle organisation (CKS2, CCP110, CKAP5 and ESCO1) and chromosome segregation (CENPE, CENPF, CENPN and SGO2). Functional validation through in vitro maturation experiments demonstrated that GTPBP4 significantly enhances the developmental competence of prepubertal goat oocytes. This enhancement occurs through mechanisms that promote cell cycle progression, organelle maturation and mRNA translation. These findings provide a detailed map of the molecular events underpinning goat oocyte maturation and offer new perspectives on the developmental strategies required for oocyte competence in prepubertal females. Translating these insights to humans, this research highlights potential fertility preservation strategies for prepubertal girls, such as ovarian tissue cryopreservation and transplantation, in vitro follicle culture, meiotic maturation and artificial ovary technologies. Moreover, the identified mechanisms have significant implications for improving reproductive efficiency in domestic animal breeding, bridging basic research and applied science.
    Keywords:  GTPBP4; adult goat; oocyte maturation; prepubertal goat; transcriptome; translatome
    DOI:  https://doi.org/10.1111/cpr.70017
  11. Biol Reprod. 2025 Feb 23. pii: ioaf037. [Epub ahead of print]
    Suppression of FOXO3 by BMP signaling contribute to the different primordial germ cell proliferation between layers and broilers.
    Yuxiao Ma, Lu Meng, Jiahui Wei, Wenhui Wu, Yun Zhang, Xuzhao Wang, Xiaotong Guo, Feiyi Wang, Yong Mao, Guiyu Zhu.
      Although all domestic chicken breeds originate from their wild relatives, the red junglefowl, they have been selectively bred for high yields in egg or meat production， or both. Some breeds are highly efficient in egg production, while others perform poorly, due to long-term selection aimed for different purposes. Female primordial germ cells (PGCs) are the precursors of eggs and the population size of PGCs will ultimately determine ovarian reserve of hens. In this study, we observed that the layers exhibit greater proliferation capacity and a higher number of PGCs compared to the broilers before meiosis. By comparing the PGC transcriptomes between layers and broilers, we identified potential genes that regulate cell proliferation. We further confirmed that FOXO3 expression is higher in broilers, where it inhibits the PGC proliferation both in vivo and in vitro. However, in layers, the upstream BMP signaling stimulate the phosphorylation of AKT and suppress FOXO3 activity. Consequently, the elevated BMP signaling and reduced FOXO3 co-operatively promote more robust PGC proliferation in layers compared to broilers and result in a greater number of PGCs in layers. Our data not only reveal molecular mechanisms underlying PGC growth, but also provide new clues to improve the laying performance in chicken.
    Keywords:  Cell proliferation; Chicken; Gene regulation; Primordial germ cells
    DOI:  https://doi.org/10.1093/biolre/ioaf037
  12. Elife. 2025 Feb 26. pii: RP100705. [Epub ahead of print]13
    Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos.
    Ryan M Finnerty, Daniel J Carulli, Akshata Hedge, Yanli Wang, Frimpong Boadu, Sarayut Winuthayanon, Jianlin Jack Cheng, Wipawee Winuthayanon.
      The oviduct is the site of fertilization and preimplantation embryo development in mammals. Evidence suggests that gametes alter oviductal gene expression. To delineate the adaptive interactions between the oviduct and gamete/embryo, we performed a multi-omics characterization of oviductal tissues utilizing bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and proteomics collected from distal and proximal at various stages after mating in mice. We observed robust region-specific transcriptional signatures. Specifically, the presence of sperm induces genes involved in pro-inflammatory responses in the proximal region at 0.5 days post-coitus (dpc). Genes involved in inflammatory responses were produced specifically by secretory epithelial cells in the oviduct. At 1.5 and 2.5 dpc, genes involved in pyruvate and glycolysis were enriched in the proximal region, potentially providing metabolic support for developing embryos. Abundant proteins in the oviductal fluid were differentially observed between naturally fertilized and superovulated samples. RNA-seq data were used to identify transcription factors predicted to influence protein abundance in the proteomic data via a novel machine learning model based on transformers of integrating transcriptomics and proteomics data. The transformers identified influential transcription factors and correlated predictive protein expressions in alignment with the in vivo-derived data. Lastly, we found some differences between inflammatory responses in sperm-exposed mouse oviducts compared to hydrosalpinx Fallopian tubes from patients. In conclusion, our multi-omics characterization and subsequent in vivo confirmation of proteins/RNAs indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner.
    Keywords:  C57BL/6J; Mus; Mus musculus; cell biology; mouse; oviduct; preimplantation embryo; sperm; superovulation
    DOI:  https://doi.org/10.7554/eLife.100705
  13. Stem Cells Cloning. 2025 ;18 15-34
    The Mammalian Oocyte: A Central Hub for Cellular Reprogramming and Stemness.
    Islam M Saadeldin, Seif Ehab, Mashan Essa F Alshammari, Aaser M Abdelazim, Abdullah M Assiri.
      The mammalian oocyte is pivotal in reproductive biology, acting as a central hub for cellular reprogramming and stemness. It uniquely contributes half of the zygotic nuclear genome and the entirety of the mitochondrial genome, ensuring individual development and health. Oocyte-mediated reprogramming, exemplified by nuclear transfer, resets somatic cell identity to achieve pluripotency and has transformative potential in regenerative medicine. This process is critical for understanding cellular differentiation, improving assisted reproductive technologies, and advancing cloning and stem cell research. During fertilization, the maternal-zygotic transition shifts developmental control from maternal factors to zygotic genome activation, establishing totipotency. Oocytes also harbor reprogramming factors that guide nuclear remodeling, epigenetic modifications, and metabolic reprogramming, enabling early embryogenesis. Structures like mitochondria, lipid droplets, and cytoplasmic lattices contribute to energy production, molecular regulation, and cellular organization. Recent insights into oocyte components, such as ooplasmic nanovesicles and endolysosomal vesicular assemblies (ELVAS), highlight their roles in maintaining cellular homeostasis, protein synthesis, and reprogramming efficiency. By unraveling the reprogramming mechanisms inherent in oocytes, we advance our understanding of cloning, cell differentiation, and stem cell therapy, highlighting their valuable significance in developmental biology and regenerative medicine.
    Keywords:  epigenetics; genome activation; oocytes; reprogramming
    DOI:  https://doi.org/10.2147/SCCAA.S513982
  14. Reproduction. 2025 Feb 01. pii: REP-24-0441. [Epub ahead of print]
    Mitochondria as Indispensable Yet Replaceable Components of Germ Plasm: Insights into PGCs Specification in Sturgeons.
    Linan Gao, Roman Franěk, Tomáš Tichopád, Marek Rodina, David Gela, Radek Šindelka, Taiju Saito, Martin Pšenička.
      While it is widely recognized that mitochondria are components of germ plasm, their specific role in the formation and specification of primordial germ cells (PGCs) remains poorly understood. Furthermore, it has not been established whether mitochondria in germ plasm possess unique characteristics essential for their function. In this study, we demonstrate that mitochondria are indispensable for PGCs development in non-teleost fishes and that their role is not dependent on their origin from germ plasm. Using sturgeon embryos, we showed that UV radiation applied to the vegetal pole effectively eliminates germ plasm, including mitochondria, and prevents PGCs formation. Remarkably, we restored germ plasm function and PGCs development by injecting mitochondria derived from donor eggs, even when these mitochondria were not originally part of the germ plasm. Transplanted mitochondria were successfully identified in larval PGCs using a fluorescent PKH26 tracer, and in interspecies transplantation experiments, their presence was confirmed using species-specific mtDNA and mtRNA primers in larvae and individual PGCs. Our findings reveal that mitochondria are critical but not germ plasm-specific determinants of PGCs formation. This study provides novel insights into the developmental pathways of germ cells and establishes a previously unrecognized flexibility in mitochondrial functionality within the germline. These findings also offer a potential method for conserving matrilineal genetics in critically endangered species like sturgeons, while simultaneously opening new avenues for studying germlines with high interspecies mitochondrial heteroplasmy and contributing to broader evolutionary and conservation biology.
    DOI:  https://doi.org/10.1530/REP-24-0441
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