bims-cebooc 2026-04-05 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–04–05
twelve papers selected by
Gabriele Zaffagnini, Universität zu Köln

Structure of the mouse cytoplasmic lattice.
Spindle pole proteins confine chromosomes to ensure their expulsion during female meiosis.
Why selection for mitochondrial quality drives the evolution of sexes.
Molecular mechanisms of folliculogenesis and oogenesis.
A Vertebrate Toxin-Antidote System That Sabotages Mouse Embryogenesis.
A spatiotemporal transcriptomic atlas of porcine (Sus scrofa) female early gonadal development.
Maternal redd1 mRNA decline triggers mTORC1 activation during the blastula-gastrula transition in zebrafish embryos.
Purifying selection during maternal inheritance of mammalian mtDNA depends on autophagy and bottleneck size.
Ovary-Derived Signals Align Protein Appetite with Oogenesis.
The glp-1 3' untranslated region regulates germline proliferation and promotes reproductive fecundity through multiple mechanisms.
The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos.
Autophagy-Independent Function of ATG-18 Is Essential for Gonadal Longevity in Caenorhabditis elegans.

Nature. 2026 Mar 31.

Structure of the mouse cytoplasmic lattice.

Pengliang Chi, Xiang Wang, Jialu Li, Jingrui Huang, Sicheng Ju, Sibei Liu, Li Yan, Yuechao Lu, Zihan Zhang, Zhuo Han, Jinhong Li, Qianqian Qi, Qingting Liu, Yiren Zeng, Li Guo, Xiaofeng Zhang, Long Gui, Dong Deng.

The fertilized egg relies almost entirely on maternal stores in the oocyte to ensure the successful initiation of development1. The cytoplasmic lattices (CPLs) in mammalian oocytes store maternal-expressed proteins and play an essential role in embryogenesis2,3. Impairing multiple CPL members leads to early embryonic arrest (EEA), resulting in infertility in mammals. However, the mechanism underlying the assembly and storage of CPLs remains largely unknown. Here, we report the cryo-EM structure of a native mouse CPL repeating unit (~ 4 MDa) at 3.74 Å resolution. This repeating unit exhibits a tripartite architecture comprising a framework, extended linkers, and a CPL core. The external framework is built from PADI6 decamers and the subcortical maternal complexes (SCMC). Two linkers formed by NLRP4F polymerize the frameworks into an extended filament. In CPL core, the epigenetic regulator UHRF1 is trapped by PADI6, UBE2D, and NLRP14 in a compact, autoinhibited conformation that prevents nuclear entry and ubiquitin ligase activity. Moreover, the CPL core stores GTP-bound α/β-tubulin heterodimers and inactive SCF E3-ubiquitin ligase components (FBXW-SKP1 complex) in a poised but restrained state. These features establish CPLs as a dynamic regulatory pool that enables rapid microtubule assembly and tightly controlled ubiquitination during the oocyte-to-embryo transition. Together, this semi-in-situ structure illuminates CPL assembly and storage-module organization, and establishes CPLs as specialized proteostasis organelles for maternal regulation in oocytes and early embryonic development.

DOI: https://doi.org/10.1038/s41586-026-10442-6
bioRxiv. 2026 Mar 25. pii: 2026.03.24.713942. [Epub ahead of print]

Spindle pole proteins confine chromosomes to ensure their expulsion during female meiosis.

Kan Yaguchi, Lifeng Chen, Abdollah Mohammadi-Sangcheshmeh, Judith Tafur, Nicole E Familiari, Edward J Grow, Michael K Rosen, Jeffrey B Woodruff.

Animal oocytes undergo highly asymmetric divisions to expel excess copies of their genome into compact cells called polar bodies. This requires tight clustering and cortical positioning of meiotic chromosomes, yet the mechanism remains incompletely understood. Using C. elegans oocytes, we found that the meiotic spindle pole protein ZYG-9/ch-TOG delocalizes from microtubules to spread along the surface of chromosomes and prevent their dispersal in meiotic anaphase. This effect was more pronounced in the absence of the spindle, where ZYG-9 formed into a micron-scale droplet that enveloped all chromosomes. Purified ZYG-9 was sufficient to bind DNA and coat reconstituted chromatin. Mutations that perturb ZYG-9-DNA binding impaired chromosome packaging into polar bodies, resulting in oocytes carrying extra chromosomes and reduced fertility. We propose that liquid-like assemblies of spindle pole proteins are repurposed as surface-acting glue to tightly package meiotic chromosomes into polar bodies, thus ensuring oocytes have the correct genome copy number.

DOI: https://doi.org/10.64898/2026.03.24.713942
Philos Trans R Soc Lond B Biol Sci. 2026 Apr 02. pii: 20250076. [Epub ahead of print]381(1947):

Why selection for mitochondrial quality drives the evolution of sexes.

Nick Lane, Andrew Pomiankowski.

  The evolution of sexes is closely tied to uniparental inheritance (UPI) of mitochondrial DNA (mtDNA), where only females transmit mtDNA. Unlike nuclear DNA, mtDNA is highly polyploid and never evolved to be part of meiotic sex. Modelling shows that UPI increases mtDNA mutational variance, enhancing selection for high-quality mtDNA and promoting the emergence of sexes from mating types in unicellular eukaryotes. Paternal control of mitochondrial transfer favours some degree of mtDNA leakage, whereas maternal control favours strict UPI, leading to sexual conflict driving turnover in transmission mechanisms. In multicellular organisms, mitotic segregation of mtDNA increases variance in gametes, again facilitating selection. Surprisingly, germline evolution seems to reflect mtDNA mutation rates: plants and sessile metazoans have low rates and produce gametes from somatic cells, while bilaterians and ctenophores with higher rates sequester germlines with restricted cell division. High mtDNA ploidy in oocytes allows early embryonic cell division without replication, reducing mutational variance across tissues and enhancing somatic fitness. Germline mtDNA quality is maintained by mitotic over-proliferation of germ cells and the selective transfer of mtDNA into primordial oocytes linked with massive apoptotic germ-cell atresia. Overall, selection for mtDNA quality elucidates the evolution of sexes and the architecture of the female germline. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.

Keywords:  Balbiani body; germline; mitochondria; mitochondrial mutation; mtDNA; oogenesis; sexes; uniparental inheritance

DOI:  https://doi.org/10.1098/rstb.2025.0076
Syst Biol Reprod Med. 2026 Dec;72(1): 211-240

Molecular mechanisms of folliculogenesis and oogenesis.

Mohamed Aboul Ezz, Ahmed Zaky Balboula.

  Folliculogenesis is a complex, multi-stage process crucial for the establishment and maintenance of female fertility through the production of a developmentally competent oocyte. Folliculogenesis, including follicular formation, activation, growth and maturation, relies on a finely tuned spatiotemporal crosstalk between germ cells, somatic cells, and the hypothalamic-pituitary-ovarian axis. This work provides a comprehensive overview of the cellular dynamics and molecular mechanisms underlying each stage of follicular development. A particular emphasis is placed on the interaction of growth factors, transcriptional networks, signaling pathways and endocrine cues that collectively govern follicular fate and oocyte quality. Disruptions in these interactions lead to emergence of pathological conditions such as premature ovarian insufficiency and age-related infertility. We further highlight the dual aspects of oocyte maturation, nuclear and cytoplasmic, as major determinants of developmental competence, and explore the role of spindle dynamics, organelle redistribution and epigenetic reprograming in this process. The bidirectional communication between oocytes and cumulus cells, mediated by paracrine signaling and jap junctions, is underscored as a pivotal regulator of oocyte metabolic activity, redox homeostasis, and meiotic competence. A better understanding of the oocyte-cumulus cell interaction offers new approaches for refining the in vitro maturation systems and improving assisted reproductive technologies. A special attention is given to the emerging use of cumulus cell-derived biomarkers for noninvasive assessment of oocyte quality and prediction of preimplantation embryo development. Taken together, this article presents an integrated framework to guide future research in reproductive biology, regenerative medicine, and fertility preservation.

Keywords:  Follicle; cumulus cells; developmental competence; meiosis; oocyte; spindle

DOI:  https://doi.org/10.1080/19396368.2026.2631558
bioRxiv. 2026 Mar 25. pii: 2026.03.04.709565. [Epub ahead of print]

A Vertebrate Toxin-Antidote System That Sabotages Mouse Embryogenesis.

Duilio M Z A Silva, Morgan Skinner, Takaya Totsuka, Takashi Akera.

Toxin-antidote (TA) systems are selfish genetic elements that bias their own inheritance by coupling a toxin that kills offspring with an antidote that specifically rescues carriers. Although widespread across bacteria, archaea, fungi, plants, and invertebrates, TA systems have not been described in vertebrates. Here we report the first vertebrate TA system, which sabotages mammalian embryogenesis. We define HEX (Homogenously staining region-mediated Embryo eXecution) as a selfish element that biases its transmission through the female mouse germline. Crosses between HEX heterozygous females and wild-type males result in selective lethality of wild-type embryos, yielding preferential survival of HEX-bearing progeny. Using mouse genetics, embryo transfer, and zygote micromanipulation, we show that HEX operates through a canonical TA mechanism: the maternally deposited toxin SP100 induces genotoxic stress in embryos, while the linked antidote SP110 selectively rescues HEX-positive embryos. Both components are core factors of the interferon signaling pathway, revealing that HEX co-opts innate immune machinery to drive transmission bias. These findings establish a vertebrate TA system and demonstrate that selfish elements can repurpose fundamental cellular pathways to violate Mendelian inheritance, with profound consequences for female fertility.

DOI: https://doi.org/10.64898/2026.03.04.709565
Commun Biol. 2026 Mar 30.

A spatiotemporal transcriptomic atlas of porcine (Sus scrofa) female early gonadal development.

Pengcheng He, Wenzhe Xia, Tianzhi Chen, Yaxuan Yan, Dengfeng Gao, Yadi Teng, Ting Zhao, Xinze Chen, Zhiqiang Feng, Runbo Li, Meng Wang, Yuwen Ke, Jianyong Han.

The early gonads of mammals contain primordial germ cells (PGCs) and gonadal somatic cells. In females, the gonadal somatic cells promote the specification of PGCs into oogonia and their entry into meiosis, which is crucial for oogenesis. Although single-cell transcriptome sequencing technology holds significant advantages in cell type identification, its inability to resolve spatial positional information substantially hampers research on communication mechanisms between germ cells and adjacent somatic cells. Here, we utilized high-resolution spatial transcriptomic technology to dissect the spatial dynamics of various cell types during the specification of PGCs into oogonia and their entry into meiosis in porcine gonads. We clarified the spatial localization of two waves of granulosa cells in the supporting cell lineage and their roles in regulating germ cell development. Furthermore, we found that interstitial and endothelial cells were predominantly located in the medullary region of the early gonads. Notably, cell-cell communication analysis revealed the critical role of BMP signaling (BMP2, BMP4 and GDF5) in driving the specification of PGCs into oogonia and their subsequent entry into meiosis. Our study provides a spatially resolved understanding of the PGC-to-oogonia specification in vivo and offers critical resources for reconstituting oogenesis in vitro.

DOI: https://doi.org/10.1038/s42003-026-09932-0
FEBS J. 2026 Apr 02.

Maternal redd1 mRNA decline triggers mTORC1 activation during the blastula-gastrula transition in zebrafish embryos.

Min-Hsuan Han, Yen-Chih Hu, Jen-Ru Chiou, Hsin-Yu Chung, Yi-Chun Ko, Chang-Tai Tsai, Jia-Hsin Chen, Chieh-En Kuo, Chun-Yu Huang, Wen-Shyong Tzou, Yung-Shu Kuan, Chin-Hwa Hu.

  During early metazoan development, maternal mRNAs and proteins stored in the egg sustain initial cellular functions. After the blastula stage, developmental control shifts to zygotic gene expression, and maternal transcripts are progressively degraded. Although mTORC1 is a central regulator of global mRNA translation and cell growth, its role in controlling maternal mRNA translation prior to gastrulation remains poorly understood. In zebrafish embryos, the mTORC1 inhibitor redd1 is abundantly expressed after fertilization but decreases following the maternal-to-zygotic transition (MZT), inversely correlating with mTORC1 activity. Overexpression of redd1 suppresses mTORC1, impairs gastrulation, and reduces translation of 5'TOP mRNAs and key regulatory genes, underscoring the necessity of relieving mTORC1 inhibition after the blastula stage. To investigate redd1 translation under conditions of low mTORC1 activity, we injected reporter mRNAs containing its 5' and 3' UTRs. The 3'UTR promoted polyadenylation and enhanced translation, while both UTRs enabled efficient reporter expression despite mTORC1 suppression, indicating that redd1 mRNA is translated independently of canonical mTORC1 pathways. Similarly, maternal mRNAs such as nanog, myca, pou5f3, and ccnb1, as well as the early zygotic transcript dharma, are translated through mTORC1-independent mechanisms. Together, these findings reveal a transient phase of mTORC1 suppression in early zebrafish embryos and demonstrate that select maternal and zygotic mRNAs bypass this regulation to ensure proper developmental progression.

Keywords:  mTORC1 activity; mTORC1‐independent translation; maternal‐to‐zygotic transition; redd1 mRNA; zebrafish embryos

DOI:  https://doi.org/10.1111/febs.70521
Autophagy. 2026 Mar 31. 1-3

Purifying selection during maternal inheritance of mammalian mtDNA depends on autophagy and bottleneck size.

Polyxeni Papadea, Nils-Göran Larsson.

  Mammalian mitochondrial DNA (mtDNA) is transmitted asexually without recombination and accumulates mutations at a high rate, which eventually should cause a mutational meltdown. Two processes operating in the maternal germline, the genetic bottleneck and purifying selection, are counteracting this decline but the exact molecular mechanisms and their possible link remain incompletely understood. To address this, we investigated the role of autophagy and mtDNA copy number in shaping purifying selection during maternal mtDNA transmission. Using a carefully designed breeding strategy in mice expressing a proofreading-deficient mitochondrial DNA polymerase, we generated animals carrying random mtDNA mutations and simultaneously introduced moderately decreased or increased mtDNA copy number, or impaired autophagy. Mutation patterns in control animals closely resembled those observed in humans, showing strong purifying selection against non-synonymous mutations, particularly in oxidative phosphorylation (OXPHOS) genes. Our recent work provides new insight by identifying autophagy as a key mediator of germline purifying selection of mtDNA. Moreover, we demonstrate that mtDNA copy number directly influences the efficiency of purifying selection, revealing that these two processes are functionally interconnected.

Keywords:  Bottleneck; maternal transmission; mitochondria; mitophagy; mtDNA mutations

DOI:  https://doi.org/10.1080/15548627.2026.2650772
bioRxiv. 2026 Mar 25. pii: 2026.03.23.711327. [Epub ahead of print]

Ovary-Derived Signals Align Protein Appetite with Oogenesis.

R R Nóbrega, A P Francisco, A M Gontijo, C Ribeiro, Z Carvalho-Santos.

Maintaining organismal homeostasis requires mechanisms that coordinate the metabolic needs of individual organs with whole animal nutrient intake. Although nutrient sensors and central pathways regulating hunger have been extensively characterized, how peripheral organ physiology influences nutrient specific appetites remains poorly understood. Here, we identify a previously unrecognized signalling axis, originated in the ovary, that modulates yeast appetite in Drosophila melanogaster . Through a targeted germline RNAi screen, we find that specific perturbations in oogenesis consistently and selectively increase yeast appetite. The manipulations increasing yeast appetite disrupt oogenesis progression, producing a shared signature of increased vitellogenic follicle accumulation and reduced number of mature (stage14) oocytes. This shift is accompanied by decreased expression of the relaxin-like hormone Dilp8, and loss of Dilp8 recapitulates the feeding phenotype. We show that this ovarian regulation of nutrient specific appetite is independent of amino acid state but requires mating, indicating integration with Sex Peptide-mediated reproductive activation. Together, our findings uncover a novel mechanism that couples oogenesis progression to nutrient selection, emphasizing the importance of the ovary as an active regulator of whole organism nutritional decisions. This work provides a conceptual framework for how reproductive tissues communicate their physiological demands to other organs and raises the possibility that analogous ovary-derived signals may shape nutrient specific appetite and metabolic states in other animals.

DOI: https://doi.org/10.64898/2026.03.23.711327
bioRxiv. 2026 Mar 25. pii: 2026.03.23.713686. [Epub ahead of print]

The glp-1 3' untranslated region regulates germline proliferation and promotes reproductive fecundity through multiple mechanisms.

Peren Coskun, Sean P Ryder.

Germline development and successful embryogenesis depend upon the post-transcriptional regulation of maternal mRNAs. In Caenorhabditis elegans , the Notch-like receptor glp-1 is necessary for germline progenitor cell proliferation in adults and anterior cell fate determination in embryos. The spatiotemporal patterning of GLP-1 protein has long served as a paradigm of maternal mRNA regulation in metazoans. The glp-1 3'UTR has been shown to be sufficient to pattern the expression of reporter genes, and multiple regulatory regions and RNA-binding protein interaction sites have been mapped. The RNA-binding proteins POS-1 and GLD-1 directly regulate glp-1 mRNA via sequence specific interactions with motifs found in the glp-1 3'UTR. The impact of mutating the endogenous glp-1 3'UTR has not been studied, and the mechanism by which POS-1 and GLD-1 mediate repression is not understood. Here, we investigate the post-transcriptional mechanisms that govern glp-1 expression, revealing that GLD-1 and POS-1 regulate this pattern through different pathways requiring different co-factors. Remarkably, mutations in the endogenous locus that disrupt either POS-1 or GLD-1 binding to the glp-1 3'UTR have minimal impact on reproductive fecundity. By contrast, a larger deletion that eliminates the binding of both has a strong effect on brood size, hatch rate, and displays an increase in the length of the germline mitotic region that corresponds with enhanced mitotic activity. Together, our results show that multiple post-transcriptional mechanisms work in concert to ensure robust GLP-1 patterning and thus maximize reproductive outcomes.

DOI: https://doi.org/10.64898/2026.03.23.713686
Nat Commun. 2026 Mar 31.

The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos.

Ling Wei, Ning Wu, Lu Chen, Tao Wang, Zhipeng Zhu, Leisheng Shi, Xi Xiang, Jie Qiao, Qiang Liu, Xiaolu Zhao, Fengbiao Mao.

Extrachromosomal circular DNA is an emerging regulatory element implicated in genomic stability and gene regulation, yet its role in preimplantation development remains elusive. Here, we report the widespread presence of extrachromosomal circular DNA in preimplantation embryos, characterized by homologous junction sequences and originating from genomic regions enriched for active histone marks and RNA Polymerase II occupancy. Functional perturbations demonstrate that RNA Polymerase II inhibition suppresses extrachromosomal circular DNA production, whereas disruption of the Fanconi anemia pathway elevates it, suggesting that transcription-replication conflicts affect its biogenesis. Notably, extrachromosomal circular DNA levels surge during major zygotic genome activation. Synthetic extrachromosomal circular DNAs carrying putative enhancers for the zygotic genome activation genes Mycn and Egfl7, and the developmental gene Emx1, significantly upregulate the expression of their respective genes upon transfection into fibroblasts and zygotes. Collectively, this study unveils the extrachromosomal circular DNA landscape in preimplantation embryos, elucidates a transcription-replication conflict mechanism underlying its generation, and establishes its regulatory potential during mammalian preimplantation development.

DOI: https://doi.org/10.1038/s41467-026-71227-z
Aging Cell. 2026 Apr;25(4): e70454

Autophagy-Independent Function of ATG-18 Is Essential for Gonadal Longevity in Caenorhabditis elegans.

Tatsuya Shioda, Ittetsu Takahashi, Makoto Horikawa, Taiichi Osumi, Takayuki Shima, Akiyo Yamauchi, Kayo Nakamura, Taeko Sasaki, Tatsuya Kaminishi, Harunori Yoshikawa, Miyuki Sato, Hidetaka Kosako, Tamotsu Yoshimori, Shuhei Nakamura.

Autophagy, a highly conserved cellular degradation process, plays essential roles in various physiological processes including aging. Though autophagy is required for lifespan extension in multiple longevity paradigms, the tissue-specific roles of autophagy-related genes (atgs) in longevity remain incompletely understood. Here, we investigate the tissue-specific requirements of atgs to promote longevity conferred by germline ablation (called gonadal longevity) using C. elegans. Remarkably, we discovered that neuronal or intestinal knockdown of atg-18, but not other atgs, specifically abolished gonadal longevity, although knockdown of all tested atgs effectively inhibited autophagic activity in these targeted tissues, implying the presence of an autophagy-independent function of ATG-18 in gonadal longevity. We demonstrated that germline deficiency triggered significant upregulation of ATG-18 in neurons and the intestine. From the proteomics analysis and subsequent screening, we found ATG-18 interacts with PCK-2, a phosphoenolpyruvate carboxykinase. PCK-2 is upregulated within the intestine of germline-deficient animals, but this depends on the non-autophagic function of ATG-18. Consistently, we showed that PCK-2 overexpression mediated longevity required ATG-18 but not its potential interacting partner to regulate autophagy, ATG-2. These findings reveal a previously unrecognized autophagy-independent role for ATG-18 in regulating lifespan in response to germline signals, expanding our understanding of how this evolutionarily conserved protein coordinates organism-wide responses to promote longevity.

DOI: https://doi.org/10.1111/acel.70454