bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–03–30
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Noncanonical phagocytosis-like SEAL establishes mammalian fertilization.
  2. Inward transport of organelles drives outward migration of the spindle during C. elegans meiosis.
  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. Two eIF4E paralogs occupy separate germ granule mRNPs that mediate mRNA repression and translational activation.
  6. EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development.
  7. Localization and function of APC15 during mouse oocyte meiotic progression.
  8. Establishing the baseline: understanding follicle activation morphometrics in multiple mammalian species.
  9. Non-viral generation of transgenic non-human primates via the piggyBac transposon system.
  10. GATA factor Serpent promotes phagocytosis in non-professional phagocytes during Drosophila oogenesis.
  11. Meiotic arrest, resumption, and TZP retraction in bovine COCs undergoing pre-IVM: lessons from a refined GV stage classification.
  12. The emergence of human primordial germ cell-like cells in stem cell-derived gastruloids.
  13. Paternal Effects in Mammalian Reproduction: Functional, Environmental, and Clinical Relevance of Sperm Components in Early Embryos and Beyond.
  1. Cell Rep. 2025 Mar 25. pii: S2211-1247(25)00234-7. [Epub ahead of print]44(4): 115463
    Noncanonical phagocytosis-like SEAL establishes mammalian fertilization.
    Naokazu Inoue, Takako Saito, Ikuo Wada.
      In many forms of sexual reproduction, only the most robust spermatozoa, which overcome multiple physiological challenges, reach the oocyte. However, the exact mechanisms of gamete recognition and fusion are unknown. In the present study, we demonstrated that with the onset of gamete recognition, oocyte microvilli form lamellipodium-like structures, activate actin polymerization, and subsequently engulf spermatozoa to initiate gamete fusion. Gamete fusion occurred via a phagocytosis-like process we termed "sperm engulfment activated by IZUMO1-JUNO linkage and gamete fusion-related factors" (SEAL). Gamete adhesion was strictly regulated by binding of sperm IZUMO1 to oocyte JUNO, while SEAL was primarily mediated by sperm DCST1/2, SPACA6, TMEM95, FIMP, and TMEM81, the essential factors for gamete fusion. Interestingly, JUNO was almost depleted from oocyte surfaces in the region where SEAL enveloped spermatozoa by microvilli without actin polymerization. SEAL formation was recapitulated using JUNO-expressing K562 lymphocytic cells rather than oocytes. Together, these findings suggest that dynamic rearrangement of membrane components facilitates SEAL prior to successful fertilization.
    Keywords:  CP: Cell biology; CP: Developmental biology; IZUMO1; JUNO; SEAL; fertilization; gamete fusion; microvilli; oocyte; oocyte tentacle; phagocytosis; spermatozoon
    DOI:  https://doi.org/10.1016/j.celrep.2025.115463
  2. Cell Rep. 2025 Mar 22. pii: S2211-1247(25)00229-3. [Epub ahead of print]44(4): 115458
    Inward transport of organelles drives outward migration of the spindle during C. elegans meiosis.
    Alma P Aquino, Wenzhe Li, Aastha Lele, Denisa Lazureanu, Megan F Hampton, Rebecca M Do, Melissa C Lafrades, Maria G Barajas, Antonio A Batres, Francis J McNally.
      Cortical positioning of the meiotic spindle within an oocyte is required to expel chromosomes into polar bodies to generate a zygote with the correct number of chromosomes. In C. elegans, yolk granules and mitochondria are packed inward, away from the cortex, while the spindle moves outward, both in a kinesin-dependent manner. The kinesin-dependent inward packing of yolk granules suggests the existence of microtubules with minus ends at the cortex and plus ends extending inward, making it unclear how kinesin moves the spindle outward. We hypothesize that the inward packing of organelles might indirectly force the spindle outward by volume exclusion. To test this hypothesis, we generate a strain in which the only kinesin consists of motor domains with no cargo-binding tail optogenetically attached to mitochondria. This mitochondria-only kinesin packs mitochondria into a tight ball and efficiently moves the meiotic spindle to the cortex, supporting the volume exclusion hypothesis.
    Keywords:  CP: Cell biology; kinesin; meiosis; meiotic spindle; oocyte
    DOI:  https://doi.org/10.1016/j.celrep.2025.115458
  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. Genetics. 2025 Mar 22. pii: iyaf053. [Epub ahead of print]
    Two eIF4E paralogs occupy separate germ granule mRNPs that mediate mRNA repression and translational activation.
    Gita Gajjar, Hayden P Huggins, Eun Suk Kim, Weihua Huang, Frederic X Bonnet, Dustin L Updike, Brett D Keiper.
      We studied translation factor eIF4E paralogs that regulate germline mRNAs. Translational control of mRNAs is essential for germ cell differentiation and embryogenesis. Messenger ribonucleoprotein (mRNP) complexes assemble on mRNAs in the nucleus, as they exit via perinuclear germ granules, and in the cytoplasm. Bound mRNP proteins including eIF4Es exert both positive and negative post-transcriptional regulation. In C. elegans, germ granules are surprisingly dynamic mRNP condensates that remodel during development. Two eIF4E paralogs (IFE-1 and IFE-3), their cognate eIF4E-Interacting Proteins (4EIPs), and polyadenylated mRNAs are present in germ granules. Affinity purification of IFE-1 and IFE-3 mRNPs allowed mass spectrometry and mRNA-Seq to identify other proteins and the mRNAs that populate stable eIF4E complexes. We find translationally repressed mRNAs (e.g. pos-1, mex-3, spn-4, etc.) enriched with IFE-3, but excluded from IFE-1. Identified mRNAs overlap substantially with mRNAs previously described to be IFE-1-dependent for translation. The findings suggest that oocytes and embryos utilize the two eIF4Es for opposite purposes on critically regulated germline mRNAs. Sublocalization within adult perinuclear germ granules suggests an architecture in which Vasa/GLH-1, PGL-1 and the IFEs are stratified, which may facilitate sequential remodeling of mRNPs leaving the nucleus. Biochemical composition of isolated mRNPs indicates opposing yet cooperative roles for the two eIF4Es. We propose that the IFEs accompany controlled mRNAs in the repressed or activated state during transit to the cytoplasm. Copurification of IFE-1 with IFE-3 suggests they may interact to move repressed mRNAs to ribosomes.
    Keywords:  4E-interacting proteins (4EIPs); Vasa; WormBase; cap-binding proteins; embryogenesis; germ cell condensates; mRNA translational control; mRNP remodeling; oogenesis
    DOI:  https://doi.org/10.1093/genetics/iyaf053
  6. 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
  7. J Mol Histol. 2025 Mar 28. 56(2): 121
    Localization and function of APC15 during mouse oocyte meiotic progression.
    Shi-Bin Chao, Ren-Ren Zhang, Qing-Yuan Sun.
      The Anaphase-Promoting Complex/Cyclosome (APC/C) is a critical regulator of cell cycle progression, with APC15 serving as an essential subunit. While the role of APC15 in mitosis is well characterized, its function during meiosis remains poorly understood. In this study, we investigated the expression, subcellular localization, and potential role of APC15 during mouse oocyte meiotic progression. Using immunofluorescence and confocal microscopy, we observed dynamic changes in APC15 localization throughout meiotic progression. Knockdown of APC15 via siRNA did not affect spindle organization, but led to meiotic arrest at metaphase I (MI) and impaired the removal of BUB3 from kinetochores, suggesting a disruption in Spindle Assembly Checkpoint (SAC) inactivation. Our results highlight the involvement of APC15 in the regulation of SAC and the transition from metaphase to anaphase in oocytes. These findings contribute to our understanding of APC15's role in meiotic regulation and provide insights into its potential impact on maintaining chromosomal stability during oocyte maturation.
    Keywords:  APC15; Meiosis; Meiotic arrest; Spindle; Spindle assembly checkpoint
    DOI:  https://doi.org/10.1007/s10735-025-10404-8
  8. 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
  9. Nat Commun. 2025 Mar 24. 16(1): 2179
    Non-viral generation of transgenic non-human primates via the piggyBac transposon system.
    Masataka Nakaya, Chizuru Iwatani, Setsuko Tsukiyama-Fujii, Ai Mieda, Shoko Tarumoto, Taro Tsujimura, Takuya Yamamoto, Takafumi Ichikawa, Tomonori Nakamura, Ichiro Terakado, Ikuo Kawamoto, Takahiro Nakagawa, Iori Itagaki, Mitinori Saitou, Hideaki Tsuchiya, Tomoyuki Tsukiyama.
      Non-human primates, such as cynomolgus monkeys, are invaluable experimental models for understanding human biology and disease. Their close genetic relationship to humans makes them essential for studying fundamental human developmental processes and disease progression. Although lentiviral methods for generating transgenic monkeys exist, several inherent technical difficulties limit their utility. To solve this problem, here we establish a non-viral method for generating transgenic cynomolgus monkeys using the piggyBac transposon system. After optimizing our protocol in mice, we show that the co-injection of piggyBac components with sperm into metaphase II-stage oocytes successfully generates transgenic monkeys expressing transgenes throughout their whole bodies. Transgene expression is observed in all examined tissue types, including germ cells, although the levels of expression vary. Insertion analysis further confirms the successful integration of the transgene. We propose that our method will be a practical non-viral protocol for generating transgenic non-human primates.
    DOI:  https://doi.org/10.1038/s41467-025-57365-w
  10. Development. 2025 Mar 26. pii: dev.204464. [Epub ahead of print]
    GATA factor Serpent promotes phagocytosis in non-professional phagocytes during Drosophila oogenesis.
    Baosheng Zeng, Haley Grayson, Jianjun Sun.
      Clearance of dying cells is essential for tissue homeostasis and requires both professional and non-professional phagocytes; however, it is unclear what promotes phagocytosis by non-professional phagocytes. Follicle cells of Drosophila egg chambers function as non-professional phagocytes to clear large germ cell debris in mid and late oogenesis, providing an excellent model for the study of non-professional phagocytes. Here we demonstrate that GATA factor Serpent (Srp) plays an indispensable role in promoting the phagocytic capacity of follicle cells in both processes. Srp is upregulated in follicle cells of degenerating mid-stage egg chambers, and its knockdown results in incomplete clearance of germ cell debris and premature follicle cell death. In addition, Srp is upregulated in stretch follicle cells and essential for clearing the nurse cell nuclei in late oogenesis. Genetic analysis reveals that Srp acts downstream of JNK signaling to upregulate the expression of the phagocytic receptor Draper (Drpr) as well as other components in the corpse processing machinery. Our findings highlight the crucial role for Srp in non-professional phagocytes during Drosophila oogenesis, which may also be conserved across species.
    Keywords:  Draper; Follicle cells; JNK; Non-professional phagocytes; Programmed cell death (PCD); Serpent
    DOI:  https://doi.org/10.1242/dev.204464
  11. Reproduction. 2025 Mar 01. pii: REP-23-0235. [Epub ahead of print]
    Meiotic arrest, resumption, and TZP retraction in bovine COCs undergoing pre-IVM: lessons from a refined GV stage classification.
    Helena Fabiana Reis de Almeida Saraiva, Juliano Rodrigues Sangalli, Luana Alves, Juliano Coelho da Silveira, Flávio Vieira Meirelles, Felipe Perecin.
      The nuclear, cytoplasmic, and molecular maturation of the mammalian oocyte is a finely orchestrated sequence of events that relies on proper cumulus-oocyte communication. Bovine oocytes enter the in vitro maturation systems at the germinal vesicle stage (GV) exhibiting four different chromatin configurations (GV0-GV3). Herein, we associate the oocyte chromatin and nuclear lamina configurations to propose a refined GV classification (GV0, GV1.1-GV1.3, GV2.1-GV2.3, and GV3.1-GV3.3). This refined GV classification system was correlated with oocyte meiosis resumption and transzonal projections (TZPs) density of COCs submitted to three IVM systems (control IVM; and a modified IVM preceded or not by a pre-IVM step). Pre-IVM resulted in lower polar body extrusion rates at 19 h IVM, albeit ~24% of the oocytes extruded their first polar body at 9 h IVM. Pre-IVM sustained 80% of oocytes meiotically arrested but altered GV distribution, reducing GV2 and increasing GV1.3 and GV3.3 categories. Pre-IVM reduced TZP densities predominantly in pre-matured GV3 and GVBD COCs. At 9 h of IVM, both groups matured in modified IVM showed lower TZP densities compared to immature and IVM control. Gene expression supports the TZP density differences, with ERK2 and PRKACA upregulation in pre-matured cumulus and in modified IVM groups at 9 h of IVM. GDF9 and BMP15 levels were similar between treated and control groups at all time points. Our findings indicate that despite the IVM system, the initial oocyte GV stage influences pre-IVM and IVM outcomes. The refined GV classification system is a useful tool to oocyte biologists.
    DOI:  https://doi.org/10.1530/REP-23-0235
  12. 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
  13. Mol Reprod Dev. 2025 Mar;92(3): e70020
    Paternal Effects in Mammalian Reproduction: Functional, Environmental, and Clinical Relevance of Sperm Components in Early Embryos and Beyond.
    Keith E Latham.
      In addition to widely recognized contributions of the paternal genome, centriole, and oocyte-activation factors, sperm deliver a wide range of macromolecules to the fertilized embryo. The impacts of these factors on the embryo, progeny, and even subsequent generations have become increasingly apparent, along with an understanding of an extensive potential for male health and environmental exposures to exert both immediate and long-term impacts on mammalian reproduction. Available data reveal that sperm factors interact with and regulate the actions of oocyte factors as well as exerting additional direct effects on the early embryo. This review provides a summary of the nature and mechanisms of paternal effects in early mammalian embryos, long-term effects in progeny, susceptibility of sperm components to diverse environmental factors, and potential approaches to mitigate adverse effects of such exposures.
    Keywords:  epigenetic; microRNA; paternal factor; semen; sperm quality; sperm transcriptome; transgenerational effects
    DOI:  https://doi.org/10.1002/mrd.70020
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