bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–02–08
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Hybrid female sterility due to cohesin protection errors in mouse oocytes.
  2. Variable partition of non-homogeneous ooplasm sets the stage for divergent potency of 2-cell stage blastomeres.
  3. Both germline cysts and the syncytium-like structure participate in oocyte differentiation in zebrafish†.
  4. Decoding the cell intrinsic and extrinsic roles of PRC2 in early embryogenesis.
  5. Early resolution of sister chromatids during C. elegans meiosis.
  6. Novel multi-omic biomarkers to combat oocyte and ovarian aging.
  7. Dysregulation of alternative splicing patterns in the ovaries of reproductively aged mice.
  8. Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations.
  9. Oocyte-specific knockout of eIF2 subunits causes apoptosis of mouse oocytes within the early growing follicles via mitochondrial dysfunctions and DNA damage.
  10. Loss of Kinesin KIF16B Disrupts Organelle Dynamics for Developmental Potential in Oocytes.
  1. Sci Adv. 2026 Feb 06. 12(6): eadx9729
    Hybrid female sterility due to cohesin protection errors in mouse oocytes.
    Warif El Yakoubi, Bo Pan, Takashi Akera.
      Hybrid incompatibility can lead to lethality and sterility of F1 hybrids, promoting speciation. The cell biological basis underlying hybrid incompatibility remains largely unknown, especially in mammals. Here, we found that female hybrids between Mus musculus domesticus and Mus spicilegus mice are sterile due to the failure of homologous-chromosome separation in oocyte meiosis, producing aneuploid eggs. This nondisjunction phenotype was driven by the mislocalization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin overprotection. The upstream kinase, BUB1, showed a higher activity in hybrid oocytes, explaining SGO2 mistargeting. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus, Peromyscus, wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility. Our work provides evidence that a major cause of human infertility may play a positive role in mammalian speciation.
    DOI:  https://doi.org/10.1126/sciadv.adx9729
  2. Mol Hum Reprod. 2026 Feb 04. pii: gaag004. [Epub ahead of print]
    Variable partition of non-homogeneous ooplasm sets the stage for divergent potency of 2-cell stage blastomeres.
    Thomas Nolte, Reza Halabian, Steffen Israel, Yutaka Suzuki, Hannes C A Drexler, Wojciech Makalowski, Georg Fuellen, Michele Boiani.
      Following fertilization in mice and humans, the first two blastomeres are not equivalent, but one produces more epiblast than the other (imbalance), therefore, they do not feature equal totipotency. Research into the causes has overlooked that the epiblast imbalance is preceded by a fertilization imbalance, since in nature, the spermatozoon fertilizes the oocyte preferentially in the animal hemisphere near the animal-vegetal midline (equator). We conceived a hypothesis that the two imbalances are linked to each other, and broke it down into testable predictions. If the two imbalances were interdependent, then changing the site of sperm entry into the oocyte should change the extent of the epiblast imbalance. Thus, we evened out the fertilization imbalance, using ICSI to fertilize mouse oocytes also in the vegetal hemisphere and the equator. Resultant embryos were split at the 2-cell stage, and the twin blastocysts originating from the sister blastomeres were analyzed. Against the similarity in mRNA levels of epiblast genes, twin blastocysts differed in epiblast function, as measured by NANOG protein expression and derivation of embryonic stem cells, and the epiblast imbalance was greater after oocyte fertilization at the equator. There is no simple way to explain the positional effect other than through differences in the molecular composition of the ooplasm, which, moreover, should also be apportioned variably at the first zygotic division. We tested these predictions by measuring the orientation of the first zygotic division regarding the ICSI site, and the composition of bisected oocytes' hemispheres using half-cell proteomics. Since we found that the hemispheres have different compositions depending on the bisection axis, and the angle of the first division is variable, we propose that the variable partition of non-homogeneous ooplasm sets the stage for the epiblast imbalance. These results revive the role of the oocyte's molecular architecture on embryogenesis in a mammalian species hitherto considered mostly regulative in development.
    Keywords:  2-cell embryo; ICSI; RNA-sequencing; blastocyst; embryo splitting; epiblast; mass spectrometry; mouse; oocyte bisection; proteome
    DOI:  https://doi.org/10.1093/molehr/gaag004
  3. Biol Reprod. 2026 Feb 02. pii: ioag026. [Epub ahead of print]
    Both germline cysts and the syncytium-like structure participate in oocyte differentiation in zebrafish†.
    Kewei Zhang, Hongmei Li, Yuhao Tao, Qichuang Wei, Leyi Chang, Xiaochun Liu.
      Oocyte differentiation occurs within germline cysts in many metazoans, where only a small number of cyst cells differentiate into oocytes, while the majority undergo apoptosis. In zebrafish, the transition of primordial germ cells (PGCs) to germline cysts has been well studied. However, the exact process by which cyst cells develop into oocytes remains unclear. Here, we analyzed the temporal and spatial characteristics of germline cysts and traced the process of oocyte differentiation in the early zebrafish gonad, by transmission electron microscopy and laser confocal microscopy. The experiments showed that germline cysts were first found at the gonadal periphery at 15 days post-fertilization (dpf) in zebrafish. No oocytes with a Balbiani body were observed within these cysts until 21 dpf. Instead, PGC daughter cells within the gonad lumen fused to form a syncytium-like structure between 15 and 16 dpf, where oocytes were formed after mitochondria and nuage aggregated into the Balbiani body since 16 dpf and were released beginning at 19 dpf. On the other hand, strong EdU-positive signals were detected in some cyst cells between 15 and 17 dpf, but not in the germ cells within the syncytium-like structure. By 21 dpf, EdU-positive cyst cells appeared in the syncytium-like structure and finally developed into individual oocytes at 25 dpf. No massive apoptosis was observed in germ cells within the syncytium-like structure. Our findings provide new insights into oocyte differentiation in zebrafish and advance our understanding of early oogenesis in vertebrates.
    Keywords:  Balbiani body; Cell apoptosis; Germline cyst; Oocyte differentiation; Syncytium-like structure; Zebrafish
    DOI:  https://doi.org/10.1093/biolre/ioag026
  4. bioRxiv. 2026 Jan 20. pii: 2026.01.20.700679. [Epub ahead of print]
    Decoding the cell intrinsic and extrinsic roles of PRC2 in early embryogenesis.
    Chengjie Zhou, Meng Wang, Zhiyuan Chen, Yi Zhang.
      Early embryogenesis is accompanied by dynamic epigenetic modifications. While such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis is less understood. Using the protein degradation tag (dTAG) system, here we decode stage- and lineage-specific functions of Eed , a core component of Polycomb Repressive Complex 2 (PRC2) in mouse early embryogenesis. Our results reveal previously underappreciated cell intrinsic and extrinsic functions of PRC2 in regulating pre-implantation and primordial germ cell (PGC) development, respectively. We demonstrate that PRC2 is required for normal maternal to zygotic transition (MZT), and epiblast (EPI) specification. Moreover, PRC2 controls proper PGC numbers in EPI through a PRC2-ESRRB-BMP4 regulatory axis in extraembryonic ectoderm (ExE). Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous function in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-TFs networks.
    DOI:  https://doi.org/10.64898/2026.01.20.700679
  5. J Cell Biol. 2026 Apr 06. pii: e202506069. [Epub ahead of print]225(4):
    Early resolution of sister chromatids during C. elegans meiosis.
    Antonia Hamrick, Ofer Rog.
      Segregating a complete set of chromosomes into the gametes relies on exchanges of genetic material that occur during meiosis. It is only exchanges that form between the homologous chromosomes (homologs), rather than between the identical sister chromatids, that enable correct chromosome segregation. Understanding how the homologs and the sisters are distinguished requires knowledge of how they are organized relative to each other. Here, we use selective labeling of a single sister in Caenorhabditis elegans to define the organization of the sister chromatids when meiotic exchanges form. We find that pairs of sisters are well separated (resolved) throughout pachytene, despite being tethered to each other along their length. Depleting the cohesin loader NIPBLSCC-2 impairs sister resolution, suggesting that an active process-likely loop extrusion-demixes the sisters. Our work shows that meiotic exchanges form in C. elegans when the sisters and homolog are roughly the same distance from one another, suggesting that repair template choice is unlikely to rely on relative proximity.
    DOI:  https://doi.org/10.1083/jcb.202506069
  6. Geroscience. 2026 Feb 03.
    Novel multi-omic biomarkers to combat oocyte and ovarian aging.
    Pawel Kordowitzki, Shakchhi Joshi, Xutong Gong, Albert Kejun Ying, Jakub Wyroba, Joanna Kochan, Marcia C Haigis.
      Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian aging will lay the cornerstone to elucidate the phenomenon of longevity in women. Here, clinical data from 400 women of various ages undergoing intracytoplasmic sperm injection (ICSI) have been analyzed, including Anti-Müllerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH) levels, the number of recovered oocytes, blastocyst rates, pregnancy rates, and live birth rates. Our analyses revealed significant differences in the aforementioned rates between patients of young and advanced age. For the biomarker analysis, we further utilised a novel predictive performance of age-associated gene expression signatures for oocyte aging, demonstrating its potential to provide molecular-level insights into oocyte quality over time. By analyzing RNA sequencing data generated from human oocytes of different ages, a genome-wide landscape of age-associated gene expression has been described. Additionally, metabolome profiling has been performed on young and reproductively aged mice, serving as a model for human ovaries. Changes in metabolites of the murine ovaries during aging have been recorded. In conjunction with traditional biomarkers, multiomics data represent a transformative approach in reproductive health, and they may offer personalised risk assessments and interventions to mitigate age-related fertility decline in women. Our metabolome profiling provides a valuable resource for elucidating the metabolomic basis of ovarian aging. Our findings offer novel insights into systemic shifts associated with oocyte and ovarian aging. This integrated approach may unlock new avenues for fertility preservation, ovarian rejuvenation, and assisted reproduction.
    Keywords:  Aging; Biomarker; Blastocyst; Metabolite; Metabolome; Oocyte; Ovary; RNA sequencing; Women
    DOI:  https://doi.org/10.1007/s11357-026-02119-9
  7. Reproduction. 2026 Feb 02. pii: xaag019. [Epub ahead of print]
    Dysregulation of alternative splicing patterns in the ovaries of reproductively aged mice.
    Adnan T Alsamaraee, Vanessa L Correll, Julius O Nyalwidhe, Pavla Brachova, Nehemiah S Alvarez.
      Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop codons, or disrupted conserved protein domains. Notably, several mitochondrial genes involved in the respiratory chain were affected. We highlight Ndufs4, a mitochondrial Complex I subunit, as a case in which aging promotes the alternative splicing of a short isoform lacking the canonical Pfam domain. Structural modeling suggests this splice variant could impair Complex I function, resulting in increased ROS production. Our data suggest a mechanistic link between splicing and mitochondrial dysfunction in the aging ovary. These findings support the model of the splicing-energy-aging axis in ovarian physiology, wherein declining mitochondrial function and adaptive or maladaptive splicing changes are intertwined. Our study reveals that alternative splicing is not merely a byproduct of aging but a dynamic, transcriptome-wide regulatory layer that may influence ovarian longevity. These insights open new avenues for investigating post-transcriptional mechanisms in reproductive aging and underscore the need to consider isoform-level regulation in models of ovarian decline.
    Keywords:  direct RNA-sequencing; ovary; post-transcriptional regulation; reproductive aging; splicing
    DOI:  https://doi.org/10.1093/reprod/xaag019
  8. EMBO Mol Med. 2026 Jan 30.
    Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations.
    Shiming Gan, Yangyang Li, Lin Yin, Xiaotong Yang, Chen Lou, Sisi Li, Mingde Lin, Xin Li, Wenchao Xu, Jiaming Zhou, Peiran Hu, Zhendong Yao, Yuan Yuan, Jianzhong Sheng, Chen Zhang, Wei Yang, Youjiang Li, Hefeng Huang.
      Oocyte activation is essential for successful fertilization and subsequent embryonic development. However, only a few disease-causing genes have been associated with sperm-derived oocyte activation failure, and the underlying molecular mechanisms and therapeutic approaches remain largely unknown. Here, we identified pathogenic mutations in HNRNPR from three infertile patients whose partners repeatedly failed to achieve transferable embryos despite undergoing both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Remarkably, artificial oocyte activation (AOA, Srcl₂) combined with ICSI successfully restored fertilization. Whole-exome sequencing revealed HNRNPR mutations shared among affected families. To establish causality, we generated a knock-in mouse model, in which males exhibited phenotypes consistent with those observed in patients. Mechanistically, ICSI with sperm from Hnrnpr-mutated mice was unable to induce normal calcium oscillations in oocytes, while spermatozoa from both humans and mice exhibited reduced expression and mislocalization of phospholipase C zeta (PLCζ). Further analyses demonstrated that hnRNPR regulates Plcz1 splicing in an m6A-dependent manner. Beyond Srcl₂ treatment, we also developed NusA-PLCζ to effectively restore oocyte activation. Collectively, these findings reveal a previously unrecognized molecular mechanism by which HNRNPR mutations cause sperm-borne oocyte activation failure and male infertility, while highlighting targeted therapeutic strategies to restore fertilization.
    Keywords:  Calcium Oscillation; Male Infertility; Oocyte Activation Failure; PLCζ; RNA Binding Protein
    DOI:  https://doi.org/10.1038/s44321-026-00374-z
  9. Cell Death Dis. 2026 Feb 02. 17(1): 196
    Oocyte-specific knockout of eIF2 subunits causes apoptosis of mouse oocytes within the early growing follicles via mitochondrial dysfunctions and DNA damage.
    Huiyu Liu, Weiyong Wang, Biao Li, Shuang Liu, Hongwei Wei, Wenjun Zhou, Tiantian Hao, Ying Wei, Xiaodan Zhang, Meijia Zhang.
      Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI). In this study, we demonstrated that the conditional knockout of eukaryotic initiation factor 2 (eIF2) subunits Eif2s1 and Eif2s2 in mouse oocytes caused oocyte apoptosis within the early growing follicles. Subsequent research indicated that the depletion of Eif2s2 in oocytes reduced the levels of mitochondrial fission-related proteins (p-DRP1, FIS1 and MFF) and increased the mRNA and protein levels of the integrated stress response (ISR)-related factors (ASNS, SLC7A1, GRB10 and PSAT1). Consistent with this, the depletion of Eif2s2 in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased mitochondrial membrane potential and ATP content, and excessive accumulation of reactive oxygen species (ROS). At the same time, the depletion of Eif2s2 in oocytes led to increased levels of DNA damage response proteins (γH2AX, p-CHK2 and p53) and proapoptotic proteins (BAX and PARP1), as well as decreased the levels of anti-apoptotic protein BCL-xL. Collectively, these findings indicate that the depletion of eIF2 subunits in mouse oocytes leads to oocyte apoptosis within the early growing follicles, attributed to the impaired translation of mitochondrial dynamics regulatory proteins and then the upregulated ROS levels and DNA damage. This study provides new insights into pathogenesis and genetic diagnosis for POI.
    DOI:  https://doi.org/10.1038/s41419-026-08449-y
  10. FASEB J. 2026 Feb 28. 40(4): e71539
    Loss of Kinesin KIF16B Disrupts Organelle Dynamics for Developmental Potential in Oocytes.
    Meng-Xiang Li, Zi-Jian Wu, Kun-Huan Zhang, Yuan-Jing Zou, Ping-Shuang Lu, Shuo-Cheng Fan, Xuan Wu, Shao-Chen Sun, Yue Wang.
      Kinesin KIF16B, as a molecular motor protein within cells, primarily utilizes energy derived from ATP hydrolysis to transport intracellular cargo along microtubules, thereby participating in material transport, organelle dynamics, and cytoskeletal organization. However, the mechanism by which KIF16B regulates the maturation process of cytoplasm in mouse oocytes remains unclear. This study was to investigate the potential role of KIF16B in modulating organelle dynamics in mouse oocytes. Our findings suggest that depletion of KIF16B impairs oocyte developmental competence following parthenogenesis, implying potential abnormalities in oocyte maturation. We observed that oocytes with diminished KIF16B exhibited disrupted mitochondrial distribution and function, and further analysis revealed that this may be due to KIF16B involvement in p-Drp1 and Fis1-mediated mitochondrial fission. Besides, impaired mitochondrial function also resulted in oxidative stress. Additionally, abnormal distribution of the ER and ER stress were observed in oocytes lacking KIF16B. This was accompanied by elevated expression of ER stress-related genes CHOP and ATF4. Concurrently, KIF16B knockdown affected the distribution and function of the Golgi apparatus, leading to abnormalities in Golgi-based vesicular transport processes. In summary, our data suggest that the kinesin KIF16B modulates organelle dynamics during oocyte maturation.
    Keywords:  KIF16B; oocyte; organelle dynamics; oxidative stress
    DOI:  https://doi.org/10.1096/fj.202504857R
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