bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–03–08
six papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.
  2. The maternal PADI6-UHRF1-UBE2D complex regulates ubiquitination during oocyte maturation and embryogenesis.
  3. Transcriptional repression of reaper by Stand still ensures female germline development in Drosophila.
  4. H3K9me2 is a determinant for the mitosis-to-meiosis transition in female germ cells.
  5. TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants.
  6. Intracellular buffering enables developmental robustness after genome doubling in C. elegans embryos.
  1. Nat Aging. 2026 Mar 03.
    Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.
    Minhoo Kim, Justin Wang, Steven E Pilley, Ryan J Lu, Alan Xu, Younggyun Kim, Minying Liu, Xueyan Fu, Sarah L Booth, Peter J Mullen, Bérénice A Benayoun.
      The decline in ovarian function with age affects fertility and is associated with increased risk of age-related diseases, including osteoporosis and dementia. Notably, earlier menopause is linked to shorter lifespan, yet the molecular mechanisms underlying ovarian aging remain poorly understood. Recent evidence suggests the gut microbiota may influence ovarian health. Here we show that ovarian aging is associated with distinct gut microbial profiles in female mice and that the gut microbiome can directly influence ovarian health. Using fecal microbiota transplantation from young or estropausal female mice, we demonstrate that heterochronic microbiota transfer remodels the ovarian transcriptome, reduces inflammation-related gene expression and induces transcriptional features consistent with ovarian rejuvenation. These molecular changes are accompanied by enhanced ovarian health and increased fertility. Integrating metagenomics-based causal mediation analyses with serum untargeted metabolomics, we identify candidate microbial species and metabolites that may contribute to the observed effects. Our findings reveal a direct link between the gut microbiota and ovarian health.
    DOI:  https://doi.org/10.1038/s43587-026-01069-3
  2. Nat Struct Mol Biol. 2026 Mar 02.
    The maternal PADI6-UHRF1-UBE2D complex regulates ubiquitination during oocyte maturation and embryogenesis.
    Jinhong Li, Yuechao Lu, Zhili Xia, Pengliang Chi, Qianqian Qi, Sibei Liu, Sicheng Ju, Jialu Li, Zihan Zhang, Zhuo Han, Qingting Liu, Wenbo Meng, Jing Chen, Xiang Wang, Li Guo, Lei Li, Wei Huang, Lunzhi Dai, Junhong Han, Shaorong Gao, Dong Deng.
      Proteostasis in mammalian oocytes is vital for successful reproduction. The cytoplasmic lattices (CPLs) of oocytes store essential maternal proteins for early embryo development. Here we show that PADI6, a core component of CPLs, forms a conserved ternary complex that we term MPU for maternal PADI6-UHRF1-UBE2D. The MPU complex regulates protein ubiquitination during oocyte maturation and early embryogenesis. We determined the cryo-electron microscopy structure of MPU and show that 86% (25/29) of clinically identified PADI6 missense variants disrupt MPU assembly, revealing a potential molecular mechanism linking dysregulation of ubiquitination on oocytes to abnormal embryonic development. Mechanistically, PADI6, with the assistance of UHRF1, sequesters UBE2D to prevent ubiquitin transfer from E2 to relevant substrate proteins, thereby suppressing the ubiquitination cascade. Therefore, our findings implicate PADI6 in the regulation of proteostasis by controlling the ubiquitination cascade, expanding our understanding of PADI6-dependent regulation of oocyte maturation and early embryogenesis.
    DOI:  https://doi.org/10.1038/s41594-026-01758-y
  3. PLoS Genet. 2026 Mar;22(3): e1012041
    Transcriptional repression of reaper by Stand still ensures female germline development in Drosophila.
    Masaya Matsui, Shinichi Kawaguchi, Toshie Kai.
      Apoptosis plays a central role in shaping tissues and preserving cellular integrity across developmental stages. In the germline, its precise regulation is critical to ensure both the elimination of aberrant cells and the maintenance of reproductive capacity. However, the molecular mechanisms that control apoptotic susceptibility in germline cells remain poorly defined. Here, we identify stand still (stil) as a female germline-specific regulator of apoptosis in Drosophila. Loss of stil leads to near-complete depletion of germline cells at the time of eclosion, associated with upregulation of the pro-apoptotic gene reaper (rpr) and activation of caspase-dependent cell death. Reporter assays in S2 cells show that Stil directly represses rpr transcription through its N-terminal BED-type zinc finger domain. The Dietera-restricted conservation of stil and rpr is consistent with a functional association. Despite the absence of stil, undifferentiated germline cells remain resistant to apoptosis. Analysis of publicly available chromatin data reveals that the rpr locus in these cells resides in a closed, H3K9me3-enriched chromatin state, suggesting a Stil-independent mode of transcriptional silencing. Together, our findings uncover two distinct mechanisms that protects the female germline from rpr-dependent apoptosis: Stil-mediated transcriptional repression that operates in both undifferentiated and differentiated germline cells, and an additional chromatin-based silencing mechanism that functions specifically in undifferentiated cells. This work provides new insights into the interplay between transcriptional and chromatin-based regulations that maintain germline cell identity and survival.
    DOI:  https://doi.org/10.1371/journal.pgen.1012041
  4. Cell Death Dis. 2026 Mar 02.
    H3K9me2 is a determinant for the mitosis-to-meiosis transition in female germ cells.
    Yanting Hu, Heyang Zhou, Lining Shi, Ke Liu, Xiangyue Meng, Xinru Guo, Liying Shan, Futeng Hu, Yongbin Liu, Teng Zhang, Yang Zhou.
      The transition from mitosis to meiosis is crucial for determining the germ cell fate and ensuring the successive production of gametes. However, the mechanisms underlying meiotic entry within the dynamic chromatin context still remain poorly understood. Herein, we demonstrate that H3K9me2, a key marker of heterochromatin formation, plays a pivotal role in the transition from mitosis to meiosis in female germ cells of mice. We show that H3K9me2 maintains high levels in female germ cells from embryonic day 13.5 to 15.5, which closely corresponds to the timing of entry into meiosis in female mice. Interestingly, the reduction of H3K9me2 levels impairs the transition from pluripotency to meiosis in female germ cells, and the role of H3K9me2 appears to act upstream of Stra8 and Dazl. Mechanistically, the multi-omics sequencing analyses of sorted germ cells reveal that H3K9me2 is specifically enriched at the promoter region of pluripotency transcription factor SOX2 and components of the ATP-dependent chromatin remodeling complex. Reduction of H3K9me2 levels results in increased chromatin accessibility, specifically for the pluripotent factor and ATP-dependent chromatin remodelers, thereby impeding the complete exit from the pluripotency progression. Hence, our findings highlight the essential role of H3K9me2 in controlling the exit from the pluripotent state and coordinating the competency of female germ cells, thereby indicating the fundamental role of chromatin remodeling processes in mitosis-to-meiosis transition. This study will provide new insights into the role of chromatin remodeling in the process of gamete production from stem cell to germ cell in vitro.
    DOI:  https://doi.org/10.1038/s41419-026-08473-y
  5. Nat Commun. 2026 Mar 05. pii: 2160. [Epub ahead of print]17(1):
    TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants.
    Zheng Gao, Qingting Liu, Lei Li, Ting Hu, Xukun Lu, Yu Wu, Dandan Qin, Xiaoxiao Wang, Chen Gu, Jinhong Li, Chengpeng Xu, Dan Zhou, Fan Zhou, YanLing Bai, Xiangjin Kang, Jianqiao Liu, Dong Deng, Lei Li.
      Pathogenic variants in NLRP7, implicated in 55% of recurrent hydatidiform mole characterized by hypomethylation at maternally methylated imprinted regions, are proposed to disrupt de novo DNA methylation in human oocytes. However, the precise mechanism remains unclear. Here, we identify TCL1A, a DNMT3A inhibitor, as an endogenous NLRP7-interacting partner. The cryo-EM structure of the NLRP7-TCL1A complex reveals its fundamental architecture. Comprehensive analysis demonstrates that the majority of recurrent hydatidiform mole-causing NLRP7 variants impair its interaction with TCL1A. Mechanistically, NLRP7 potentially safeguards oocyte methylome by sequestering TCL1A in the cytoplasm, thereby preventing its nuclear entry and subsequent suppression of DNMT3A-mediated de novo methylation. Combining in silico predictions and interaction analysis, we identify L766R as a pathogenic variant. These findings propose a cytoplasmic regulatory mechanism governing nuclear DNA methylation, explaining the hypomethylation pathogenesis in NLRP7 variant-associated recurrent hydatidiform mole.
    DOI:  https://doi.org/10.1038/s41467-026-69744-y
  6. Cell Rep. 2026 Mar 02. pii: S2211-1247(26)00083-5. [Epub ahead of print] 117005
    Intracellular buffering enables developmental robustness after genome doubling in C. elegans embryos.
    Miaoling Yang, Yuchuan Bai, Ziyi Wang, Zhuo Du.
      Whole-organism polyploidy is widespread across species, yet how embryogenesis adapts to genome doubling remains unclear. Here, we present a systematic single-cell comparison of embryogenesis between de novo-induced tetraploid and diploid C. elegans embryos, integrating live imaging, lineage tracing, phenotypic quantification, and transcriptomic profiling. Despite elevated transcript levels, slower proliferation, and altered cell architecture, tetraploid embryos develop with high fidelity, producing cell numbers, lineage patterns, fate specification, and tissue morphogenesis virtually indistinguishable from diploids. In tetraploids, transcriptional output increases proportionally with cell volume, resulting in largely stable transcript concentrations, although specific gene sets show divergence, suggesting additional layers of regulation. The importance of this scaling is underscored by their heightened sensitivity to size perturbations. Meanwhile, a sublinear volume increase relative to genome content raises DNA-to-volume ratios, correlating with delayed proliferation, suggesting potential physical or regulatory constraints on volume expansion. Our findings reveal how intracellular scaling strategies support accurate embryogenesis following genome doubling.
    Keywords:  C. elegans; CP: developmental biology; CP: genomics; cell cycle; cell lineage; cell size; developmental robustness; embryogenesis; gene expression; polyploidy; single-cell analysis; tetraploid
    DOI:  https://doi.org/10.1016/j.celrep.2026.117005
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