bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–10–04
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction.
  2. A β-importin supports fusome growth and distribution in Drosophila ovarian germ cells.
  3. Biological significance of centromeric satellite asymmetry in female meiosis.
  4. Chromatin remodeling coordinates chromosome compaction, synaptonemal complex architecture and meiotic crossing-over.
  5. Multifaceted and evolutionarily dynamic interactions between Caenorhabditis elegans SPO-11 and its cofactors ensure proper formation of meiotic DNA double-strand breaks.
  6. Traveling Waves Enhance Transport during Cytoplasmic Streaming in Drosophila Oogenesis.
  7. High-throughput functional characterization of enhancers in totipotent-like cells.
  8. Does the postmenopausal ovary still matter?
  9. Nuclear envelope buffering of cytoskeletal force stabilizes chromosome interactions in C. elegans meiosis.
  10. An atlas of the C. elegans starvation response reveals that transcription is necessary to initiate transcriptional silencing in quiescent primordial germ cells.
  11. Exploring the impact of lipid metabolism in mammalian oocytes and its implications for assisted reproductive technology outcomes.
  1. Nat Metab. 2026 Oct 02.
    Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction.
    Longsen Han, Yiqiu Wu, Jiashuo Li, Yujia Chen, Ling Li, Teng Wang, Ming Chen, Shanshan Wang, Congyang Li, Guolian Ding, Jingyu Li, Hongzheng Sun, Zhonghua Shi, Qiang Wang.
      Maternal obesity predisposes offspring to metabolic disease, yet how oocytes transmit this risk remains unclear. Here, we show that maternal obesity induces locus-specific DNA methylation changes in oocytes to drive intergenerational metabolic dysfunction in a tissue-specific and sex-specific manner. Among these, a subset of metabolic genes, notably Hnf1α, Thra and Pdk4, exhibited persistent intergenerational methylation and transcriptional dysregulation. Although these methylation marks were erased during embryogenesis, H3K36me2 enrichment was retained at the loci, suggesting a potential chromatin-associated cue for methylation re-establishment. Single-CpG analysis identified regulatory landmarks correlating with gene expression, and conserved hypermethylation of HNF1A and THRA was also detected in oocytes from women with obesity. Using methylation-edited mouse models, we further demonstrated that targeted oocyte hypermethylation at Hnf1α enhanced hepatic gluconeogenesis in offspring, whereas Pdk4 hypermethylation impaired glucose tolerance, both in a female-biased manner. Together, our findings provide direct causal evidence that germline methylation at defined loci can programme intergenerational metabolic dysfunction, highlighting the preconception period as a critical window for potential intervention in humans.
    DOI:  https://doi.org/10.1038/s42255-026-01617-6
  2. Genetics. 2026 Sep 30. pii: iyag267. [Epub ahead of print]
    A β-importin supports fusome growth and distribution in Drosophila ovarian germ cells.
    Amanda M Powell, Anna E Williams, Elizabeth T Ables.
      Germline cysts, or interconnected groups of germ cells, promote the synchronization of gamete development in vertebrates and invertebrates. In the Drosophila ovary, cyst formation is accompanied by growth of the fusome, a unique endoplasmic reticulum-like organelle. Although structural components of the fusome have been characterized, much less is known about the genetic factors that control fusome growth and distribution between germ cells. Here, we identify the β-importin, Tnpo-SR, as a regulator of fusome morphogenesis in germline stem cells (GSCs) and cysts. Although Tnpo-SR does not aggregate at fusomes or centrosomes, Tnpo-SR null mutants fail to form proper fusomes and depletion of Tnpo-SR alters fusome deposition and reduces fusome accumulation in GSCs. We demonstrate that Tnpo-SR-depletion disrupts microtubule organization and subcellular localization of the microtubule-associated protein Asp during interphase. Finally, we provide data suggesting that Tnpo-SR genetically interacts with microtubule-associated proteins and the cytoskeletal protein Hts, and likely functions indirectly and upstream of these key regulators of fusome formation, cyst architecture, and oocyte specification. Taken together, these data provide compelling evidence linking nuclear transport machinery to fusome morphogenesis and germline cyst development in Drosophila.
    Keywords:  Tnpo-SR; cyst; germline; oogenesis; reproduction
    DOI:  https://doi.org/10.1093/genetics/iyag267
  3. Biol Reprod. 2026 Sep 28. pii: ioag216. [Epub ahead of print]
    Biological significance of centromeric satellite asymmetry in female meiosis.
    Deepanshu Kumar, Michael A Lampson.
      Centromeres ensure faithful chromosome segregation, yet the satellite arrays typically underlying these loci exhibit remarkable variation in sequence, organization, and size across individuals and species. Recent advances in long-read genome assemblies and experimental model systems have begun to reveal that this diversity is not simply tolerated but can directly influence centromere function during female meiosis. Asymmetry between centromeric satellite arrays of homologous chromosomes can lead to asymmetries in kinetochore proteins and spindle interactions, biased chromosome orientation on the spindle, and ultimately non-Mendelian inheritance by centromere drive. Emerging evidence further suggests that centromeric satellite asymmetry can increase meiotic chromosome segregation errors and aneuploidy, particularly in the context of small arrays. In this review, we discuss recent progress linking centromeric satellite variation with meiotic chromosome behavior, centromere drive, and segregation fidelity.
    Keywords:  CENP-A chromatin; Centromere asymmetry; centromere drive; female meiosis; meiotic segregation errors; satellite array
    DOI:  https://doi.org/10.1093/biolre/ioag216
  4. Res Sq. 2026 Sep 10. pii: rs.3.rs-10849354. [Epub ahead of print]
    Chromatin remodeling coordinates chromosome compaction, synaptonemal complex architecture and meiotic crossing-over.
    Joao Matos, Nathan Palmer, Uladzislava Khauratovich, Laurine Dal Toe, Felix Hartmann, Anzhela Pavlova, Sushil Khanal, Rajvi Patel, Vasiliki Petroulaki, Viktoria Bláhová, Neil Hunter, Thomas Robert, Anton Goloborodko.
      Crossing-over between maternal and paternal chromosomes during meiosis relies on the maturation of recombination intermediates within the synaptonemal complex (SC). These events unfold within a hierarchically organized environment, in which linear arrays of chromatin loops are anchored to the axes of meiotic chromosomes. Yet, how chromatin organization is integrated with crossover maturation remains poorly understood. Here, we identify the nucleosome remodeler CHD1 as a previously unrecognized component of the mammalian SC. CHD1 localizes at the interface of synapsed homologs through direct interaction with the SC central-element protein SYCE1 and regulates meiotic chromosome organization. Conditional depletion of CHD1 in meiocytes increases chromatin accessibility at recombination hotspots, disrupts chromosome compaction, and reduces the spatial separation between homolog axes. These meiosis-specific structural defects are accompanied by impaired stabilization of crossover-promoting factors at incipient crossover sites. Together, our findings demonstrate that CHD1-mediated nucleosome remodeling shapes meiotic chromosome organization across scales, creating a chromatin environment that supports crossover maturation and fertility.
    DOI:  https://doi.org/10.21203/rs.3.rs-10849354/v1
  5. bioRxiv. 2026 Aug 02. pii: 2026.07.30.741518. [Epub ahead of print]
    Multifaceted and evolutionarily dynamic interactions between Caenorhabditis elegans SPO-11 and its cofactors ensure proper formation of meiotic DNA double-strand breaks.
    Keita Kameda, Li Zhou, Nowa Matsubayashi, Carlos Mario Rodriguez-Reza, Lin Meng, Xuan Li, Tomoki Yoshioka, Aya Sato-Carlton, Peter Mark Carlton.
      DNA double-strand breaks (DSBs) generated during meiotic prophase by the topoisomerase-like protein SPO11 are essential to create crossovers between homologous chromosomes. Since crossovers are required to biorient chromosomes at the first meiotic division, DSB formation is essential for meiosis in most sexually-reproducing organisms. Since excess DSBs have the potential to destabilize the genome, SPO-11 activity must be strictly regulated by many cofactors. Recent studies have established that SPO11 must dimerize to cut DNA, whereas soluble SPO11 and SPO11-TOPOVIBL complexes are predominantly monomeric (1-3). This contrast suggested that a major role of SPO11 cofactors could be to promote SPO11 dimerization, through means such as increasing local concentration or co-orienting SPO11 protomers. However, the mechanism of this regulation is not well-understood. Here, by taking advantage of phylogenomic analysis in the nematode genus Caenorhabditis, we show that the conserved cofactor DSB-1Rec114 evolved to replace TOPOVIBL function in C. elegans. We provide genetic and biochemical evidence that multiple interactions between SPO-11 and DSB-1 stabilize protein complex formation and promote SPO-11 dimerization. Our results shed light on the regulatory mechanism of programmed DSB formation, which ensures crossover formation and meiotic chromosome segregation while protecting genomic stability.
    DOI:  https://doi.org/10.64898/2026.07.30.741518
  6. ArXiv. 2026 Sep 22. pii: arXiv:2609.26656v1. [Epub ahead of print]
    Traveling Waves Enhance Transport during Cytoplasmic Streaming in Drosophila Oogenesis.
    Olenka Jain, David B Stein, Reza Farhadifar, Elizabeth R Gavis, Stanislav Y Shvartsman, Michael J Shelley.
      Cytoplasmic streaming is believed crucial to large developing cells, such as oocytes, where flow provides a much faster route to transport and mixing of cellular components than molecular diffusion. Molecular motors carrying cargoes on cytoskeletal elements are known to drive streaming in a variety of biological systems and, in Drosophila oocytes, cell-spanning vortical flows are tied to kinesin motors moving on dense beds of microtubules. Recent theories and simulations suggest such streaming self-organizes through interacting microtubules, motors, and flow. Whether these theoretically derived flows are adequate to the tasks of transport and mixing has been unclear. Here we report on new observations of coherent waves traveling persistently through microtubule beds during streaming, and investigate their impact on fluid transport and mixing. Leveraging recent advances in simulating the complex fluid-structure problems of cellular environments, we probe a biophysical model set in an oocytal geometry. Our simulations identify previously unknown waving states that show concordance with our experimental observation and the capacity for functional transport and mixing.
  7. Nat Commun. 2026 09 01. pii: 10399. [Epub ahead of print]17(1):
    High-throughput functional characterization of enhancers in totipotent-like cells.
    Lingyue Yang, Tianran Peng, Yating Zhu, Xuzhao Zhai, Boyan Huang, Hai Zhou, Dafeng Tao, Ling Li, Tao Zhang, Yunxia Cao, Jiekai Chen, Dan Liang, Jiangping He, Man Zhang.
      Zygotic genome activation (ZGA) marks the initial transcription event in embryogenesis, yet the cis-regulatory mechanism remains unclear. Here, utilizing massively parallel reporter assays, we functionally dissect enhancers across mouse genome in DUX-induced 2C-like cells (2CLCs). Through integrated analysis with epigenomic and transcriptomic data from 2CLCs and 2C embryos, active enhancers in totipotent cells are depicted. Among them, a notable proportion of promoters exhibit enhancer activities, showing elevated active chromatin features and correlating with enhanced gene expression during ZGA. Transcription factors preferentially enriched at enhancer-promoter regions play critical roles in regulating ZGA and early embryonic development. Furthermore, only half of the MT2_Mm exhibit enhancer activities in 2CLCs. Notably, 2CLC enhancers augment transcription in 2C embryos. Finally, deleting enhancer regions in both 2CLCs and 2C embryos, together with dCas9-KRAB-MeCP2-mediated CRISPRi in vitro, collectively underscores their crucial role in facilitating transcription of ZGA genes. These findings advance our comprehension of the cis-regulatory mechanism governing ZGA process.
    DOI:  https://doi.org/10.1038/s41467-026-77311-8
  8. Science. 2026 Oct;394(6819): 44-45
    Does the postmenopausal ovary still matter?
    Michael B Stout, Francesca E Duncan.
      Ovaries may influence health long after their reproductive function ends.
    DOI:  https://doi.org/10.1126/science.aeh7496
  9. bioRxiv. 2026 Sep 10. pii: 2026.09.07.749962. [Epub ahead of print]
    Nuclear envelope buffering of cytoskeletal force stabilizes chromosome interactions in C. elegans meiosis.
    Rachel Nenstiel, Chenshu Liu.
      Meiosis requires coordination between chromosome and nuclear envelope (NE) dynamics. Cytoskeletal forces transmitted through the NE via Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes drive chromosome movement but can also compromise nuclear integrity if not properly balanced. Here, we identify the conserved inner nuclear membrane protein NEMP-1 as a key regulator that contributes to buffering of excessive force at the meiotic NE in Caenorhabditis elegans . NEMP-1 localizes to the NE throughout meiotic prophase and becomes enriched at the NE in nuclei with a weakened nuclear lamina. Simultaneous depletion of NEMP-1 and the lamin protein LMN-1 results in premature nuclear collapse and defects in chromosome synapsis and homolog pairing. These phenotypes depend on excessive dynein-mediated forces acting on a compromised NE. Furthermore, analysis of homolog pairing in the absence of synapsis revealed that NEMP-1 and LMN-1 contribute to the stabilization of synapsis-independent homolog interactions at the NE. Together, our findings reveal that excessive force at the NE can destabilize homolog interactions, and support a model in which NEMP-1 and LMN-1 cooperatively buffer cytoskeletal forces to maintain nuclear integrity while stabilizing chromosome interactions during meiosis.
    One-sentence summary: Two nuclear envelope proteins synergize to maintain homolog interactions and meiotic nuclear integrity.
    DOI:  https://doi.org/10.64898/2026.09.07.749962
  10. bioRxiv. 2026 Sep 08. pii: 2026.09.04.749554. [Epub ahead of print]
    An atlas of the C. elegans starvation response reveals that transcription is necessary to initiate transcriptional silencing in quiescent primordial germ cells.
    Jingxian Chen, Sharan Surya, Rojin Chitrakar, Jenna R Valley, Marcos Francisco Perez, L Ryan Baugh.
      Starvation profoundly impacts development, but how different tissues respond to starvation is unclear. We generated a cellular atlas of gene expression in fed and starved C. elegans L1 larvae. We identified 79 cell types in both conditions, and we detected ∼98% of protein-coding genes, 44% of which were differentially expressed. Starvation affected translation-related genes across the animal, and most 'housekeeping' genes were downregulated. However, tissue-specific patterns of differential expression, transcription factor activity, and GO term enrichments are widespread, suggesting tissue-specific gene regulatory mechanisms and functional consequences. We inferred tissue-specific effects on transcription factor activity, identifying known and novel putative nutrient-dependent transcriptional regulators. Surprisingly, we found extensive transcription in starved primordial germ cells (PGCs), which are known to hyper-compact their chromatin and silence transcription during L1 starvation. We validated PGC transcription of aak-1/AMPK , and we showed that zygotic aak-1/AMPK is required for PGC chromatin hyper-compaction, supporting reproductive success upon recovery. This work provides a valuable resource characterizing nutritional control of transcription in an animal, and it reveals that transcription of aak-1/AMPK is necessary to silence transcription in quiescent PGCs.
    DOI:  https://doi.org/10.64898/2026.09.04.749554
  11. JBRA Assist Reprod. 2026 Oct 02.
    Exploring the impact of lipid metabolism in mammalian oocytes and its implications for assisted reproductive technology outcomes.
    Romualdo Sciorio, Federica Cariati, Luca Tramontano, Mariagrazia Orsi, Nishad Chimote, Carlo Alviggi, Steven Fleming.
      In assisted reproductive technolog, both invasive and non-invasive criteria are widely used to identify oocytes and embryos with high developmental potential, with the ultimate goal of improving live birth rates. Since the earliest applications of in vitro fertilization in the 1970s, non-invasive assessment methods have played a central role in evaluating oocyte and embryo competence. These approaches rely primarily on morphological analysis, in-cluding assessment of the mature cumulus-oocyte com-plex (COC), the presence and morphology of the first polar body, zona pellucida thickness, characteristics of the peri-vitelline space, and cytoplasmic appearance. Oocyte quali-ty is a fundamental determinant of successful fertilization, subsequent embryo development, implantation, and the establishment of a healthy term pregnancy. The follicular environment also plays a crucial role in regulating oocyte maturation and developmental competence. Within the follicle, the COC functions as a coordinated unit in which the oocyte regulates its growth and development through metabolic interactions with the surrounding cumulus and granulosa cells. During maturation, the oocyte's energy requirements are largely met through the β-oxidation of fatty acids stored in lipid droplets (LDs). These LDs under-go spatial redistribution during maturation, which may be associated with changes in the oocyte's viscoelastic prop-erties. Alterations in lipid metabolism within the COC can impair oocyte developmental competence and may help explain the reduced survival of some oocytes after intra-cytoplasmic sperm injection. This review critically exam-ines the relationship between the follicular environment and oocyte metabolism, with particular emphasis on lipid metabolism and oocyte and embryo quality. It also dis-cusses established non-invasive markers of oocyte quality and emerging approaches based on oocyte biomechanical properties that may be associated with embryo viability, implantation, and term pregnancy.
    Keywords:  assisted reproductive technology; bio-mechanical properties; lipid metabolism; non-inva-sive assessment; oocyte morphology; oocyte quality
    DOI:  https://doi.org/10.5935/1518-0557.20260064
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