bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–06–22
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes.
  2. H2A.Z is essential for oocyte maturation and fertility in female mouse.
  3. Nuances in the control of separase activity between mitosis and meiosis.
  4. IRE1α RNase activity is critical for early embryo development by degrading maternal transcripts.
  5. Ovarian remodeling and aging-related chronic inflammation and fibrosis in the mammalian ovary.
  6. Crossover patterning through condensation and coarsening of pro-crossover factors.
  7. Protease-mediated activation of Par2 elicits calcium waves during zebrafish egg activation and blastomere cleavage.
  8. Myosin VI is expressed in developing ovarian follicles in Drosophila but is not essential for effective oogenesis.
  9. Ovarian aging at single-cell resolution: current paradigms and perspectives.
  10. In preprints: rethinking the foundations of the ovarian reserve.
  1. Nat Struct Mol Biol. 2025 Jun 13.
    H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes.
    Hailiang Mei, Ryoya Hayashi, Chisayo Kozuka, Mami Kumon, Haruhiko Koseki, Azusa Inoue.
      Mammalian oocytes establish a unique landscape of histone modifications, some of which are inherited by early embryos. How histone variants shape the maternal histone landscape remains unknown. Here we map histone H2A variants in mouse fully grown oocytes (FGOs) and find that H2A.Z forms broad domains across intergenic regions, along non-canonical H3K4me3 (ncH3K4me3). During oocyte growth, H2A.Z progressively transitions from an active promoter-rich, canonical distribution to a non-canonical broad distribution (ncH2A.Z). Depletion of H2A.Z in oocytes partially impairs ncH3K4me3 formation and causes severe defects in meiotic progression, which resemble Mll2-knockout oocytes. Conversely, depletion of ncH3K4me3 by Mll2 knockout also causes a reduction of ncH2A.Z in FGOs. Thus, our study suggests that ncH2A.Z and ncH3K4me3 reinforce each other to form functional oocytes.
    DOI:  https://doi.org/10.1038/s41594-025-01573-x
  2. Nat Struct Mol Biol. 2025 Jun 13.
    H2A.Z is essential for oocyte maturation and fertility in female mouse.
    Qianhua Xu, Chunyi Huang, Jia Ming, Xukun Lu, Ling Liu, Zhenhai Du, Zhen Chen, Jie Na, Guohong Li, Yunlong Xiang, Yu Zhang, Wei Xie.
      Oocyte maturation is essential for both gametogenesis and early development, when large amounts of transcripts are produced without DNA replication. Histone variants, which can be incorporated at cis-regulatory elements in a replication-independent manner, are naturally suited for such regulation. However, their roles during mammalian oocyte maturation remain elusive. Here we show that oocyte-specific depletion of H2A.Z, an evolutionarily conserved histone variant, in female mice results in profound epigenetic and transcriptional alterations, impedes resumption of oocyte meiosis II and causes infertility. Mechanistically, H2A.Z in mouse oocytes is incorporated into chromatin at active promoters and putative enhancers. Interestingly, H2A.Z is depleted from CG-rich silenced promoters, including poised Polycomb target genes, in fully grown oocytes (FGOs), unlike what occurs in growing oocytes, early embryos and mouse embryonic stem cells. In FGOs, the presence of H2A.Z correlates with histone acetylation, except in regions marked by DNA methylation and H3K36me3. Depletion of H2A.Z leads to impaired activities of a subset of promoters and enhancers, correlated with defective gene expression. Consistent with a role in gene activation, H2A.Z in FGOs is widely acetylated at the promoters and enhancers. Together, our findings uncover an essential role of H2A.Z in mammalian oocyte maturation and female fertility.
    DOI:  https://doi.org/10.1038/s41594-025-01580-y
  3. PLoS Biol. 2025 Jun;23(6): e3003206
    Nuances in the control of separase activity between mitosis and meiosis.
    Martin Anger.
      Mammalian oocytes are prone to chromosome segregation errors, which frequently lead into aneuploidy and pregnancy loss. A new study in PLOS Biology addresses the role of the Mad2/SGO2 complex in the control of separase activity in these cells during meiosis.
    DOI:  https://doi.org/10.1371/journal.pbio.3003206
  4. Nucleic Acids Res. 2025 Jun 06. pii: gkaf520. [Epub ahead of print]53(11):
    IRE1α RNase activity is critical for early embryo development by degrading maternal transcripts.
    Chao Li, Yong-Peng Tan, Di Gao, Ruibao Su, Ke Xu, Shu-Chen Liu, Xu-Feng Li, You-Hui Lu, Li-Tao Yi, Guang Wang, Xiang-Hong Ou, Tie-Gang Meng, Qing-Yuan Sun.
      During maternal-to-zygotic transition, oocytes and embryos undergo massive maternal mRNA degradation. Three key events are related to RNA degradation: oocyte meiotic resumption, fertilization, and zygotic genome activation (ZGA). In this study, we unexpectedly discover that the UPR (unfolded protein response) protein IRE1α is critical for post-fertilization maternal messenger mRNA (mRNA) degradation. IRE1α is specifically expressed from the metaphase II oocytes to four-cell embryos, with its translation dependent on the ERK1/2 pathway. Oocyte-specific deletion of the IRE1α RNase domain resulted in female infertility, characterized by embryonic developmental arrest at the one-cell or two-cell stage, and failure to degrade maternal mRNAs destined for elimination. Using IRE1α-Flag knock-in mouse model and LACE-seq, as well as in vitro analysis, we show that IRE1α can directly bind and cleave maternal mRNAs after fertilization. Moreover, IRE1α-mediated mRNA decay is essential for ZGA and histone modifications. This study unveils an important function of IRE1α in early embryonic development through regulated IRE1α-dependent decay, independent of the canonical IRE1α-XBP1 signaling pathway, thereby revealing a novel molecular mechanism underlying maternal mRNA degradation triggered by fertilization.
    DOI:  https://doi.org/10.1093/nar/gkaf520
  5. J Ovarian Res. 2025 Jun 18. 18(1): 133
    Ovarian remodeling and aging-related chronic inflammation and fibrosis in the mammalian ovary.
    Yuanyuan Zhu, Heming Sun, Ting Gao, Shengdi Hou, Yuebo Li, Ying Xu, Qingxia Zhang, Dingqing Feng.
       BACKGROUND: The female ovary undergoes constant follicular atresia from birth, as well as ovulation and corpus luteum (CL) regression during reproductive age, leading to recurrent ovarian remodeling and ultimately resulting in ovarian aging. However, aging-related cellular and molecular changes in the ovary remain poorly explored.
    RESULTS: Using ovarian transcriptomics, we characterized the changes in gene expression in the ovaries of young (2-month-old), middle-aged (6-month-old) and old (12-month-old) mice. Our analyses revealed that the stromal cell markers THY1 and CD44 were significantly upregulated, whereas the markers of oocytes, granulosa cells and theca cells were markedly downregulated in old mice; thus, endocrine dysfunction occurred. We also found that MAPK pathway- and inflammation response-related genes were enriched and that the populations of Tregs, macrophages and NK cells notably decreased in aged ovaries, which was confirmed by flow cytometry. However, during superovulation, the proportions of macrophages and NK cells steadily increased as the follicles developed and ovulated, whereas the proportion of macrophages sharply decreased after ovulation. We further verified these ovarian changes in specific cell markers and rate-limiting enzymes for steroid hormone synthesis by immunohistochemistry (IHC) and collagen deposition by Masson's trichrome staining in pre- and postmenopausal women.
    CONCLUSIONS: These results from clinical samples demonstrated that aging-associated changes were similar to those observed in mice and were strongly correlated with the age of the woman. Therefore, this report provides critical insights into aging-related cellular and molecular changes in the ovary.
    Keywords:  Chronic inflammation; Fibrosis; Ovarian aging; Ovarian remodeling
    DOI:  https://doi.org/10.1186/s13048-025-01715-1
  6. Nat Cell Biol. 2025 Jun 19.
    Crossover patterning through condensation and coarsening of pro-crossover factors.
    Liangyu Zhang, Weston Stauffer, Chenshu Liu, Hengyi Shao, Noor Abuzahriyeh, Rui Jiang, David Zwicker, Xing Liu, Xuebiao Yao, Abby F Dernburg.
      Meiotic recombination mixes genetic information from parental genomes, creating unique combinations of alleles. During meiotic prophase, each homologue pair must undergo at least one crossover to segregate faithfully. Only a few recombination intermediates become crossovers, and these are widely spaced or limited to one per chromosome pair. Mechanisms that regulate crossover number and spacing remain poorly understood. Here we show that, in Caenorhabditis elegans, 'recombination nodules', protein assemblies that stabilize recombination intermediates and promote crossover formation, assemble in part through biomolecular condensation and are stabilized by CDK-2 kinase activity. We further demonstrate that essential components of these nodules move along the synaptonemal complex (SC) and do not freely exchange between SCs in the same nucleus. Our findings reveal that recombination nodules behave as active droplets and support a model in which coarsening of these droplets via protein translocation along liquid crystalline SCs underlies crossover patterning.
    DOI:  https://doi.org/10.1038/s41556-025-01688-9
  7. PLoS Biol. 2025 Jun;23(6): e3003181
    Protease-mediated activation of Par2 elicits calcium waves during zebrafish egg activation and blastomere cleavage.
    Jiajia Ma, Tom J Carney.
      Successful initiation of animal development requires activation of the egg immediately prior to fusion of gamete pronuclei. In all taxa, this is initiated by waves of calcium transients which transverse across the egg. Calcium waves also occur at cleavage furrows during later blastula cytokinesis. Calcium is released from the endoplasmic reticulum through activation of inositol-1,4,5-trisphosphate (IP3) receptors. Only a subset of the mechanisms employed to generate IP3 during vertebrate egg activation are defined, with strong evidence that other critical mechanisms exist. Serine proteases have been long implicated in egg activation and fertilization. Here, we report that treatment of zebrafish eggs with serine protease inhibitors leads to defective calcium wave propagation and failed egg activation. We further show that mutation of zebrafish Protease-activated receptor 2a (Par2a) also results in severe disruption of egg activation, leading to failed chorion elevation and ooplasmic segregation. Milder par2a mutants progress further, but then show abnormal blastomere cleavage. We observed that par2a mutants show decreased amplitude and duration of calcium transients. Restoring Ca++ or direct injection of IP3 ligand rescues egg activation aborted by either serine protease inhibitor treatment or by mutation of Par2a. We thus show that serine protease activity is a critical regulator of IP3 and subsequent calcium wave amplification during zebrafish egg activation, and link this to intracellular calcium release via the protease receptor, Par2a. This constitutes a novel signaling pathway critical for successful fertilization.
    DOI:  https://doi.org/10.1371/journal.pbio.3003181
  8. Front Cell Dev Biol. 2025 ;13 1535117
    Myosin VI is expressed in developing ovarian follicles in Drosophila but is not essential for effective oogenesis.
    Robert Lenartowski, Jakub Ostrowski, Anna Suwińska, Anna Richert, Przemysław Zakrzewski, Magdalena Izdebska, Wioletta Arendt, Kathryn G Miller, Marta Lenartowska.
      Myosin VI is the only actin-based motor known to move toward the minus end of actin filaments. This protein is involved in many different cellular processes, such as endocytosis, autophagy, secretion, and regulation of actin organization and dynamics. Myosin VI has also been suggested to play an important role in collective migration of border cells and egg chamber development during Drosophila oogenesis. Here we show for the first time that myosin VI is expressed in Drosophila germarium as well as in early ovarian follicles, especially in the developing oocyte. As oogenesis progresses, the level of myosin VI in maturing egg chambers decreases, but this protein is present both in the nascent border cell cluster, during its delamination from the epithelium, and then during the early stages of border cell migration. However, we demonstrate that myosin VI deficiency in border cells, or even complete lack of this protein in myosin VI mutant do not inhibit border cell migration. Moreover, deficiency/lack of myosin VI does not cause any serious defects in ovarian morphology, egg chamber morphogenesis, oogenesis, and egg development. Thus we conclude that myosin VI is not a key player in Drosophila oogenesis.
    Keywords:  Drosophila oogenesis; RNAi; binary system; border cell migration; cell/molecular biology; myosin VI mutant; transgenic flies
    DOI:  https://doi.org/10.3389/fcell.2025.1535117
  9. Ageing Res Rev. 2025 Jun 15. pii: S1568-1637(25)00153-9. [Epub ahead of print] 102807
    Ovarian aging at single-cell resolution: current paradigms and perspectives.
    Junzhi Liang, Shurui Gai, Xinni Na, Jia Hu, Zhongyu Zhao, Duo Zi, Zhijing Na, Wenyan Gao, Fangfang Bi, Da Li.
      Ovarian failure is a key event in female reproductive aging, resulting in the depletion of follicular reserve and a decline in fertility. In addition, it triggers systemic pathological changes, including osteoporosis and cardiovascular disease, due to decreased estrogen levels. Despite extensive study, mapping senescent ovarian cells is challenging due to the multicellular composition and heterogeneity of the ovary. In the past decade, single-cell resolution technologies have provided new insights into ovarian aging by enabling the molecular characterization of individual cells. Here, we comprehensively review the application of these technologies in delaying ovarian aging and promoting reproductive health. We summarize their value in uncovering cell-type-specific mechanisms and their potential uses in the research of ovarian aging, ultimately deepening our understanding of its pathogenesis and molecular basis.
    Keywords:  Applications; Ovarian aging; Single-cell resolution
    DOI:  https://doi.org/10.1016/j.arr.2025.102807
  10. Development. 2025 Jun 15. pii: dev204939. [Epub ahead of print]152(12):
    In preprints: rethinking the foundations of the ovarian reserve.
    Andrea Rix, Binyam Mogessie.
      
    DOI:  https://doi.org/10.1242/dev.204939
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