bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–03–01
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Intergenerational Transmission of Metabolic Changes in Oocytes From Aged Mice.
  2. THAP1 is a maternal effect factor required for the first cell cycle via Rrm1 in early mouse embryos.
  3. To Be or Not to Be an Oocyte: Msps/XMAP215 Controls Oocyte Cell Fate in the Drosophila Ovary.
  4. Replication Protein A1 is essential for DNA damage repair during mammalian oogenesis†.
  5. Developmentally programmed nuclear pore complex replacement enables oocyte specification.
  6. BOLL-Containing Aggregates Mediate the Translational Regulation During Human Oogenesis.
  7. Maternal O-GlcNAc Transferase Is Required for the Asymmetry of Epigenetic Modifications in Mouse Zygotes.
  8. Reduced Akr1b7 signaling drives ovarian aging and reproductive dysfunction.
  9. Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila.
  10. Altering dosage of meiotic crossover-associated RING finger proteins affects crossover number and interference in Drosophila.
  11. Mitochondria aggregation patterns during human oocyte maturation.
  12. Nascent transcriptome of embryonic genome activation reveals a regulatory axis linking transcriptional priming to early lineage specification in mouse embryos.
  13. Polycomb Repressive Complex 1 primes non-growing oocytes for growth and early embryogenesis.
  1. Aging Cell. 2026 Mar;25(3): e70426
    Intergenerational Transmission of Metabolic Changes in Oocytes From Aged Mice.
    Hafsa Gulzar, Richard Musson, Simona Bisogno, Lulu Alluhaibi, Alexey Maximenko, Ewelina Bik, Małgorzata Barańska, Joanna Depciuch, Grażyna E Ptak.
      The increase in maternal age of pregnancies is a global phenomenon that may have wide-ranging implications for the future health of the next generations. We have previously shown that oocytes from females at advanced maternal age (AMA F0) accumulate intracytoplasmic lipid droplets (LDs), and that oxidative changes to lipids in oocytes from AMA F0 mice are maintained in preimplantation embryos. Here we explore whether oxidative changes are transmitted to the foetus, and what effects this has on neonatal and adult organ development, and the transgenerational inheritance of these changes. First, we show increased antioxidants in lipid-rich organs (liver and brain) of AMA-derived prenatal mice (AMA F1), indirectly showing increased oxidative stress. Then, we provide evidence of metabolic reprogramming in adult offspring of AMA and the accumulation of lipids in AMA-derived third generation (AMA F3) mouse oocytes. In particular, we demonstrate the accumulation of retinoids and other mediators of oxidative phosphorylation (OXPHOS) in AMA F0 and AMA F3 oocytes. Altogether, an altered oxidative metabolism of AMA F0 oocytes may constitute a base of oxidative changes in the organs of offspring and of their transgenerational inheritance to AMA F3 oocytes. Our findings indicate a remodelling of lipid homeostasis in oocytes of female mice derived from AMA great-grandmothers and highlight the need to take a closer look at the inheritance of metabolic changes from mothers of advanced age into their offspring.
    DOI:  https://doi.org/10.1111/acel.70426
  2. EMBO Rep. 2026 Feb 23.
    THAP1 is a maternal effect factor required for the first cell cycle via Rrm1 in early mouse embryos.
    Qiang Fan, Xi Wu, Yanna Dang, Lijun Dong, Wenying Wang, Feng Kong, Lijuan Wang, Xukun Lu, Boyang Liu, Shuyan Ji, Wei Xie.
      Maternal effect genes (MEGs) produce factors that accumulate in oocytes and play critical roles in embryo development. Mutations of MEGs are frequently linked to reproductive and congenital disorders. The majority of identified mammalian MEGs encode epigenetic factors and RNA regulators. Here, we identify a MEG encoding the transcription factor Thanatos-associated protein 1 (Thap1). Thap1 is highly expressed in mouse oocytes and early embryos. Oocyte-specific deletion of Thap1 results in delayed progression of mouse embryos from the 1-cell to the 2-cell stage and 1-2-cell arrest, accompanied by defective zygotic genome activation (ZGA) and strongly impaired female fertility. Mechanistically, THAP1 activates a critical subset of genes in oocytes, including Rrm1, which produces ribonucleotide reductase required for generating deoxynucleotide triphosphates (dNTPs). Low-input metabolome profiling across 7 stages during the oocyte-to-embryo transition shows gradual, THAP1-dependent dNTP accumulation that peaks in MII oocytes. Overexpression of Rrm1 in zygotes almost fully restores the 2-cell progression and ZGA in Thap1 maternal-knockout embryos. Our findings identify THAP1 as a key maternal effector critical for the earliest stage of mammalian development.
    Keywords:  Cell Cycle; MEG; RRM1; THAP1; dNTP
    DOI:  https://doi.org/10.1038/s44319-026-00712-9
  3. bioRxiv. 2026 Feb 12. pii: 2026.02.10.705054. [Epub ahead of print]
    To Be or Not to Be an Oocyte: Msps/XMAP215 Controls Oocyte Cell Fate in the Drosophila Ovary.
    Wen Lu, Margot Lakonishok, Hannah Neiswender, Graydon B Gonsalvez, Vladimir I Gelfand.
      Cell fate determination, the process by which cells commit to specific identities, is fundamental to development. Oocyte specification in Drosophila provides an excellent model to dissect these molecular mechanisms. In the Drosophila ovary, 16 interconnected germline cells arise through four mitotic divisions with incomplete cytokinesis. Among them, the two oldest cells become pro-oocytes, and one is selected to develop into the oocyte while maintaining diploidy; the remaining 15 differentiate into nurse cells and enter endoreplication. Previously, we showed that Mini spindles (Msps), a microtubule polymerase and homolog of XMAP215, is essential for oocyte maintenance. Here, we report that Msps/XMAP215 is expressed early in development, with both mRNA and protein enriched in the pro-oocytes prior to oocyte specification. Knockdown of Msps prevents oocyte specification, leading to egg chambers with 16 nurse cells. Loss of Msps also disrupts the accumulation of the oocyte marker Orb and the microtubule minus-end binding protein Patronin/CAMSAP, both critical for oocyte specification. Remarkably, optogenetic recruitment of Msps is sufficient to increase microtubule polymerization and promote Orb accumulation in nurse cells, suggesting that Msps activity is sufficient to drive oocyte fate determination. Furthermore, we show that Msps associates with the germline-specific organelles, spectrosome and fusome, and becomes asymmetrically distributed among sister cells, allowing the two pro-oocytes to inherit higher levels of Msps than their siblings. Together, we propose a model in which Msps-mediated microtubule polymerization provides the pro-oocyte with a competitive advantage, initiating a positive feedback loop that involves dynein-dependent transport of msps mRNA to reinforce oocyte specification.
    Teaser: A self-reinforcing cytoskeletal feedback loop selects a single egg cell from a cluster of interconnected germ cells.
    DOI:  https://doi.org/10.64898/2026.02.10.705054
  4. Biol Reprod. 2026 Feb 27. pii: ioag049. [Epub ahead of print]
    Replication Protein A1 is essential for DNA damage repair during mammalian oogenesis†.
    Xiaosu Miao, Rui Guo, Andrea Williams, Kaylei Wong, Vienna Rivard, Catherine Lee, Jun Ma, P Jeremy Wang, Wei Cui.
      Persistence of unrepaired DNA damage in oocytes is detrimental and may cause genetic aberrations, miscarriage, and infertility. RPA, a single-stranded DNA (ssDNA)-binding complex, is essential for various DNA-related processes. Here we report that RPA plays a novel role in DNA damage repair during postnatal oocyte development after meiotic recombination. To investigate the role of RPA during oogenesis, we inactivated RPA1 (replication protein A1), the largest subunit of the heterotrimeric RPA complex, specifically in oocytes using two germline-specific Cre drivers (Ddx4-Cre and Zp3-Cre). We find that depletion of RPA1 leads to the disassembly of the RPA complex, as evidenced by the absence of RPA2 and RPA3 in RPA1-deficient oocytes. Strikingly, severe DNA damage occurs in RPA1-deficient GV-stage oocytes. Loss of RPA in oocytes triggered the canonical DNA damage response mechanisms and pathways, such as activation of ATM, ATR, DNA-PK, and p53. In addition, the RPA deficiency causes chromosome misalignment at metaphase I and metaphase II stages of oocytes, which is consistent with altered transcript levels of genes involved in cytoskeleton organization in RPA1-deficient oocytes. Absence of the RPA complex in oocytes severely impairs folliculogenesis and leads to a significant reduction in oocyte number and female infertility. Our results demonstrate that RPA plays a previously unrecognized role in DNA damage repair during mammalian folliculogenesis.
    Keywords:  DNA damage; chromosome alignment; female fertility; folliculogenesis; oocyte-specific conditional knockout
    DOI:  https://doi.org/10.1093/biolre/ioag049
  5. bioRxiv. 2026 Feb 16. pii: 2026.02.13.705775. [Epub ahead of print]
    Developmentally programmed nuclear pore complex replacement enables oocyte specification.
    Shruti Venkat, Tram Nguyen, Cecilia Blangini, Michelle Pollak, Karen Schindler, Maya Capelson, Prashanth Rangan.
      Oocytes endow embryos with molecular machinery essential for development, but not all maternal components are inherited indiscriminately. In Drosophila, surveillance pathways eliminate defective mitochondria and aberrant RNAs from the maternal pool. Whether stable nuclear structures, like nuclear pore complexes (NPCs), are similarly curated remains unknown. Here, we uncover a developmentally programmed NPC turnover pathway that renews NPCs during oocyte specification. NPC levels decline through a combination of passive dilution, driven by deferred nucleoporin expression, and active degradation mediated by the ESCRT-III/Vps4 pathway. This clearance is counterbalanced by subsequent de novo NPC synthesis. Failure to turn over NPCs results in aberrantly persistent germ cell gene expression and defective oocyte specification. These findings establish NPC renewal as a critical step in oocyte identity establishment and maternal provisioning.
    DOI:  https://doi.org/10.64898/2026.02.13.705775
  6. Cell Prolif. 2026 Feb 25. e70181
    BOLL-Containing Aggregates Mediate the Translational Regulation During Human Oogenesis.
    Ying Li, Lingya Mao, Boyuan Liang, Longxin Xie, Wenpei Xiang, Kehkooi Kee.
      Human oocyte meiosis utilises a specialised translational control strategy to coordinate meiotic progression, mediated through dynamic regulation of mRNA stores. While germ cell-specific RNA-binding proteins (RBPs) are known to orchestrate this post-transcriptional programme, the mechanistic basis of RBP-mediated cell fate specification remains elusive. Here, we demonstrate that BOLL, a Deleted in Azoospermia (DAZ) family protein, forms protein aggregates during meiotic prophase to drive translational reprogramming in human oogenesis. We determined that BOLL enhances the translation efficiency of cell cycle regulators, as demonstrated by integrative translatome-transcriptome analysis combined with RNA immunoprecipitation sequencing. We also revealed the functional interaction network of BOLL with core translation machinery components through its conserved DAZ-containing domain. Crucially, we identified SDS-resistant protein aggregates as a structural signature of BOLL in human oocyte-like cells, demonstrated by semi-denaturing electrophoretic analysis. Using human foetal ovarian tissues and an hESC-derived oogenesis model, we delineate a paradigm wherein BOLL-containing aggregates exert spatiotemporal control over cell cycle genes during meiosis prophase. These findings reveal that protein aggregates of gametogenesis-specific RBPs constitute an evolutionarily conserved mechanism in mammalian reproductive regulation.
    Keywords:  human BOLL protein; oogenesis; protein aggregate; translational regulation
    DOI:  https://doi.org/10.1111/cpr.70181
  7. FASEB J. 2026 Feb 28. 40(4): e71592
    Maternal O-GlcNAc Transferase Is Required for the Asymmetry of Epigenetic Modifications in Mouse Zygotes.
    Haoxue Wang, Dan Liu, Shinnosuke Honda, Shuntaro Ikeda.
      After fertilization in mammals, there is an epigenetic asymmetry reflected by differences in DNA demethylation and histone modifications between female and male pronuclei (FPN and MPN, respectively). Based on its expression level and amount, we investigated the role of maternal O-GlcNAc transferase (OGT), a key enzyme mediating O-GlcNAcylation, in regulating this asymmetry. By using a specific small-molecule inhibitor and small interfering RNA (siRNA)-mediated knockdown of OGT during oocyte maturation in mice, we evaluated the downstream effects on epigenetic modifications and early developmental capability. OGT inhibition significantly reduced fertilization rates and led to developmental arrest at the zygote or 2-cell stage, whereas the siRNA-mediated decrease of Ogt mRNA had less or no significant effect on preimplantation development. Immunostaining analyses revealed that OGT inhibition reduced 5-hydroxymethylcytosine levels in MPN, attributed to a reduction in Tet methylcytosine dioxygenase 3. In contrast, FPN showed delayed epigenetic changes, with the loss of 5-methylcytosine protection mediated by H3K9me2. Moreover, OGT inhibition increased histone methylation levels in MPN and disrupted epigenetic and size asymmetry between FPN and MPN. These alterations suggest that maternal OGT regulates multiple layers of epigenetic reprogramming in early zygotes. Taken together, these findings suggest that maternal OGT is essential for maintaining epigenetic asymmetry between parental pronuclei, primarily by modulating DNA demethylation and histone methylation in MPN.
    Keywords:  DNA demethylation; O‐GlcNAc transferase; embryonic development; epigenomics; histone; oocyte; zygote
    DOI:  https://doi.org/10.1096/fj.202503577RR
  8. iScience. 2026 Feb 20. 29(2): 114719
    Reduced Akr1b7 signaling drives ovarian aging and reproductive dysfunction.
    Keishiro Isayama, Kenji Watanabe, Masato Ohtsuka, Seisuke Kimura, Tomoaki Murata, Takeshi Honda, Masataka Asagiri, Shun Sato, Hiroshi Tamura, Norihiro Sugino, Yoichi Mizukami.
      Natural ovarian aging is associated with a progressive decline in female fertility. Here, we comprehensively analyzed RNA expression during ovarian aging in mice during the estrous cycle following ovulation stimulation. The transient activation of the Aldo-keto reductase Akr1b7 pathway observed in the ovaries of young mice was absent in older mice. Akr1b7 -/- mice exhibit attenuated oocyte Akt activation, impaired follicular development, an increased proportion of ovulated immature oocytes, and decreased litter size. The estrous cycle is extended in Akr1b7 -/- mice due to a prolonged diestrous stage, driven by sustained progesterone levels. This elevation in progesterone was associated with the reduced expression of Cyp17a1, a progesterone-metabolizing enzyme in the Akr1b7-positive theca cell layers. Together, these findings identify Akr1b7 as a regulator of ovarian signaling, hormone homeostasis, and reproductive function, with the disruption of this pathway producing phenotypes associated with declining fertility.
    Keywords:  Endocrine regulation; Endocrine system physiology; Endocrinology; Female reproductive endocrinology; Health sciences
    DOI:  https://doi.org/10.1016/j.isci.2026.114719
  9. Nat Genet. 2026 Feb 24.
    Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila.
    Noura Maziak, Yuchen Zhang, Fabian Groll, Haley E Brown, Alla Madich, Yadwinder Kaur, Melissa M Harrison, Jian Zhou, Juan M Vaquerizas.
      How chromatin conformation relates to chromatin state remains a central challenge in genome regulation. Here we present Pico-C, a low-input Micro-C approach that enables high-resolution, temporally resolved three-dimensional genome mapping during early Drosophila embryogenesis. Contrary to a prevailing view of a disorganized genome before zygotic genome activation (ZGA), we uncover a dynamic and ordered emergence of chromatin loops during pre-ZGA nuclear cycles. Spatial autocorrelation analysis points to context-dependent regulatory influences on chromatin. Notably, inhibition of transcriptional elongation has site-specific effects, retaining some early loops while weakening insulation at active promoters, suggesting distinct regulatory dependencies. Machine learning models trained on sequence features identify orthogonal, motif-specific contributions to architecture. Co-depletion of the pioneer factors Zelda and GAF leads to factor-specific perturbations in chromatin architecture, further highlighting a modular regulatory logic in genome establishment. Together, our findings reveal that early genome organization is orchestrated by an interplay of overlapping yet separable regulatory inputs.
    DOI:  https://doi.org/10.1038/s41588-026-02503-3
  10. bioRxiv. 2026 Feb 19. pii: 2026.02.18.706578. [Epub ahead of print]
    Altering dosage of meiotic crossover-associated RING finger proteins affects crossover number and interference in Drosophila.
    Emerson Frantz, Priscila Santa Rosa, Susan McMahan, Jeff Sekelsky.
      Crossovers play a critical role in ensuring correct reductional segregation of homologous chromosomes in the first meiotic division. Crossing over is initiated by formation of DNA double-strand breaks (DSBs), but the number of DSBs is greater than the number of crossovers. Which recombination sites become crossovers, versus being repaired as non-crossovers, is not random, but is subject to several crossover patterning phenomena, including crossover assurance and crossover interference. One current model for crossover designation proposes that crossover-associated RING finger proteins (CORs) undergo the biophysical process of coarsening, in which larger accumulations continue to get larger and smaller accumulations go away. Genetic and cytological studies of the three CORs in Drosophila melanogaster , Vilya, Narya, and Nenya, are consistent with this model. In females heterozygous for a deletion of vilya , fewer doublecrossovers are observed. Conversely, crossovers are elevated in females carrying a duplication of vilya and in females coordinately overexpressing Vilya , Narya, and Nenya. These findings support a model in which crossover designation occurs through coarsening of COR proteins within the synaptonemal complex.
    DOI:  https://doi.org/10.64898/2026.02.18.706578
  11. Hum Fertil (Camb). 2026 Dec;29(1): 2635860
    Mitochondria aggregation patterns during human oocyte maturation.
    Adrian Ellenbogen, Gal Bachar, Paz Gili, Ofer Fainaru.
      Animal studies have demonstrated that mitochondrial distribution within the oocyte is closely associated with nuclear and cytoplasmic maturation. Aberrant mitochondrial localisation patterns have been linked to incomplete cytoplasmic maturation and reduced developmental competence. The aim of this study was to characterise the dynamics of mitochondrial distribution in human oocytes across different stages of maturation. Using discarded oocytes from patients undergoing intracytoplasmic sperm injection (ICSI) we analysed the concentration of mitochondria and their distribution patterns. Homogeneously diffuse, centrally located, and peripheral distributions were detected in mature metaphase II (MII), immature metaphase I (MI) and immature germinal vesicle (GV) oocytes, respectively. Of the MII oocytes, 61% presented an evenly diffuse pattern and of the GV oocytes, 53% presented a peripheral distribution. The mean mitochondrial density increased significantly from 278,501 ± 65,989 area units in GV oocytes to 352,340 ± 37,942 in MII oocytes (p = 0.003). For cytoplasmic occupancy, which followed a non-normal distribution, the median percentage increased from 73.7% (IQR: 66.9%-78.7%) in GV oocytes to 100.0% (IQR: 84.8%-100.0%) in MII oocytes (p < 0.001). Upon maturation, human oocytes demonstrate an increase in mitochondria density and cytoplasm occupancy. Importantly, the mitochondria tend to be located mainly at the periphery in immature oocytes, achieving a more diffuse homogeneous pattern as the oocyte matures. This pattern of distribution may play an important role in cytoplasmic maturation of human oocytes and their further development.
    Keywords:  Mitochondria; distribution; maturation; oocyte cytoplasm
    DOI:  https://doi.org/10.1080/14647273.2026.2635860
  12. Nucleic Acids Res. 2026 Feb 24. pii: gkag173. [Epub ahead of print]54(5):
    Nascent transcriptome of embryonic genome activation reveals a regulatory axis linking transcriptional priming to early lineage specification in mouse embryos.
    Yue Hu, Yuxiang Wang, Maosheng Ye, Yuanlin He, Zhangyi Ouyang, Chao Ren, Tianyin Miao, Siqi Wang, Ou Zhong, Li Liu, Wenjie Shu, Ran Huo.
      Embryonic genome activation (EGA) marks a critical developmental transition, yet its regulatory architecture remains incompletely defined. Here, we employed optimized low-input SLAM-seq (thiol(SH)-linked alkylation for the metabolic sequencing) to map the temporal hierarchy of nascent transcription during mouse EGA. We uncovered patterns of transcriptional priming characterized by pre-activated genes (PAGs) with permissive chromatin states, followed by pronounced accumulation of PAGs-encoded proteins in blastocysts, suggesting that EGA memory propagates from early transcriptional activation to later lineage commitment. Furthermore, Integrative analysis nominated two-cell nascent transcription factors (TFs) as candidate regulators of the first lineage specification. Functional investigations demonstrated KLF17 as a key TF linking EGA to the first lineage specification via regulation of PAGs transcription. KLF17 deficiency led to the failure of transcriptional activation in approximately half of PAGs at the two-cell stage. Our work provides a detailed framework for decoding mammalian EGA and offers insights into how embryonic transcriptional priming is coordinated with early cell fate specification.
    DOI:  https://doi.org/10.1093/nar/gkag173
  13. Cell Res. 2026 Feb 23.
    Polycomb Repressive Complex 1 primes non-growing oocytes for growth and early embryogenesis.
    Mengwen Hu, Yasuhisa Munakata, Yu-Han Yeh, Raissa G Dani, Han Wang, Neil Hunter, Richard M Schultz, Satoshi H Namekawa.
      
    DOI:  https://doi.org/10.1038/s41422-026-01232-w
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