bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–06–29
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Single-cell and spatiotemporal profile of ovulation in the mouse ovary.
  2. Single-cell migration in development - Lessons from germ cells.
  3. PLK-1 suppresses centrosome maturation and microtubule polymerization to ensure faithful oocyte meiosis.
  4. A direct interaction between the RNA-binding proteins Staufen and Tm1-I/C in the oskar mRNA transport complex.
  5. Retrotransposon 3S18 forms self-protective aggregates and prolongs mid-oogenesis.
  6. HELQ Maintains Genome Stability of Primordial Germ Cells by Inhibiting LINE-1 Expression.
  7. Oocyte transport against fluid flow to the fertilization site in mice: contributions of cilia beating and peristalsis†.
  8. Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.
  9. Replication competition drives the selective mtDNA inheritance in Drosophila ovary.
  10. Comprehensive mathematical modeling of age-dependent oocyte quality and quantity for predicting live birth rate.
  1. PLoS Biol. 2025 Jun;23(6): e3003193
    Single-cell and spatiotemporal profile of ovulation in the mouse ovary.
    Ruixu Huang, Caroline E Kratka, Jeffrey Pea, Cai McCann, Jack Nelson, John P Bryan, Luhan T Zhou, Daniela D Russo, Emily J Zaniker-Gomez, Achla H Gandhi, Alex K Shalek, Brian Cleary, Samouil L Farhi, Francesca E Duncan, Brittany A Goods.
      Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.
    DOI:  https://doi.org/10.1371/journal.pbio.3003193
  2. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00013-4. [Epub ahead of print]164 1-27
    Single-cell migration in development - Lessons from germ cells.
    Jan Schick, Laura Ermlich, Lucas Kühl, Dennis Hoffmann, Erez Raz.
      Primordial germ cells (PGCs) migrate to associate with somatic cells to form the gonad, generate gametes and thereby ensure fertility. This chapter presents the mechanisms underlying single-cell migration performed by PGCs in various organisms, such as zebrafish, Drosophila, and the mouse models. This review introduces the principles of cell motility, factors controlling directed migration, and the effects of interactions between migrating cells and their environment. Specifically, it discusses passive and active migration mechanisms, the roles of guidance cues, and of interactions with different tissues that influence PGC migration. Comparative analysis of the process in different organisms reveals conserved and distinct strategies for motility and directed migration. The presented mechanisms contribute to broader understanding of cell migration, highlighting PGCs as a useful in vivo model for studying the principles governing the movement of cells within tissues.
    Keywords:  Actin; Bleb; Cell migration; Cell polarity; Chemokine; Germ cells; Motility; PGC
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.01.002
  3. J Cell Biol. 2025 Sep 01. pii: e202503080. [Epub ahead of print]224(9):
    PLK-1 suppresses centrosome maturation and microtubule polymerization to ensure faithful oocyte meiosis.
    Juhi G Narula, Sarah M Wignall.
      Sexual reproduction relies on meiosis, a specialized cell division program that produces haploid gametes. Oocytes of most organisms lack centrosomes, and therefore chromosome segregation is mediated by acentrosomal spindles. Here, we explore the role of Polo-like kinase 1 (PLK-1) in Caenorhabditiselegans oocytes, revealing mechanisms that ensure the fidelity of this unique form of cell division. Previously, PLK-1 was shown to be required for nuclear envelope breakdown and chromosome segregation in oocytes. We now find that PLK-1 is also required for establishing and maintaining acentrosomal spindle organization and for preventing excess microtubule polymerization in these cells. Additionally, our studies revealed an unexpected new role for this essential kinase. While PLK-1 is known to be required for centrosome maturation during mitosis, we found that either removal of PLK-1 from oocytes or inhibition of its kinase activity caused premature recruitment of pericentriolar material to the sperm-provided centrioles following fertilization. Thus, PLK-1 suppresses centrosome maturation during oocyte meiosis, which is opposite to its role in mitosis. Taken together, our work identifies PLK-1 as a key player that promotes faithful acentrosomal meiosis in oocytes and demonstrates that its catalytic activity is required for carrying out these important roles.
    DOI:  https://doi.org/10.1083/jcb.202503080
  4. Cell Rep. 2025 Jun 25. pii: S2211-1247(25)00677-1. [Epub ahead of print]44(7): 115906
    A direct interaction between the RNA-binding proteins Staufen and Tm1-I/C in the oskar mRNA transport complex.
    Thomas Gaber, Thomas Monecke, Julia Grabowski, Bernd Simon, Tobias Williams, Vera Roman, Jeffrey Chao, Janosch Hennig, Anne Ephrussi, Dierk Niessing, Simone Heber.
      In the Drosophila female germline, oskar messenger RNA is transported on microtubules from the nurse cells to the posterior pole of the oocyte, where it is translated. Transport of oskar transcripts from the nurse cells into the oocyte requires dynein, while localization of the mRNAs within the oocyte to the posterior pole is dependent upon kinesin-1. Staufen, a double-stranded RNA (dsRNA)-binding protein, has been shown to bind the oskar mRNA transport complex in the oocyte and inactivate dynein; however, it remains unclear how kinesin is activated. Here, using surface plasmon resonance, nuclear magnetic resonance spectroscopy, and RNA imaging within egg chambers, we demonstrate that Staufen directly interacts with Tropomyosin1-I/C (Tm1), a non-canonical kinesin adaptor. This work provides molecular evidence of how Staufen integrates into the oskar messenger ribonucleoprotein (mRNP) complex.
    Keywords:  CP: Molecular biology; NMR; RNA localization; RNA-binding proteins; biophysics; motor proteins; protein-protein interactions
    DOI:  https://doi.org/10.1016/j.celrep.2025.115906
  5. Cell Rep. 2025 Jun 24. pii: S2211-1247(25)00685-0. [Epub ahead of print]44(7): 115914
    Retrotransposon 3S18 forms self-protective aggregates and prolongs mid-oogenesis.
    Dan Shen, Yaqian Xu, Qi Shi, Chongyang Li, Zhe Meng, Qiuju Wen, Chenhui Wang, Kun Dou.
      Transposons are prevalent across nearly all species due to their capacity to mobilize in the host genome. However, their products may begin to affect the host before integration occurs. Here, we identified that the activation of transposons results in significantly smaller mid-stage oocytes and prolonged mid-oogenesis of Drosophila. Notably, one specific long terminal repeat (LTR) retrotransposon, 3S18, primarily contributes to this phenotype. We found that 3S18 mRNA and its integrase form micrometer-scaled ribonucleoprotein aggregates at cell-cell bridges during these stages. Interestingly, mutants that suppress the formation of these RNP aggregates substantially reduce 3S18 mRNA levels, suggesting that 3S18 aggregates serve functional importance in protecting the retrotransposon products. Live imaging reveals that the accumulation of 3S18 RNP aggregates obstructs host material transportation, resulting in prolonged mid-oogenesis. Finally, forcefully extending oogenesis significantly enhances 3S18 propagation. Our study highlights the unique characteristics of 3S18 and its impact on host development. It may shed light on studies of other parasitic elements, including viruses.
    Keywords:  3S18; CP: Developmental biology; CP: Molecular biology; LTR; aggregate; retrotransposon; transportation
    DOI:  https://doi.org/10.1016/j.celrep.2025.115914
  6. FASEB J. 2025 Jun 30. 39(12): e70720
    HELQ Maintains Genome Stability of Primordial Germ Cells by Inhibiting LINE-1 Expression.
    Lili Cao, Jiayi Ren, Zhaojie Kong, Mengchun Hu, Yaxuan Zhang, Zi-Jiang Chen, Yingying Qin, Yajuan Yang, Shidou Zhao.
      The DNA helicase HELQ is involved in homologous recombination repair, interstrand cross-link repair, and replication stress response. Its functional defects are associated with infertility and abnormal gametogenesis. However, the specific mechanisms of HELQ in the development of germ cells remain to be elucidated. Here, we uncovered that HELQ deficiency led to proliferation defects of primordial germ cells (PGCs) in mouse embryos, thus compromising the establishment of reproductive reserve. Mechanistically, we found that HELQ interacted with the H3K9me3 demethylase KDM4B, and the absence of HELQ led to a marked increase in both total and chromatin-bound protein levels of KDM4B, resulting in reduced H3K9me3 levels in the region of the retrotransposon LINE-1, which triggered its high expression and subsequently caused DNA damage accumulation. Moreover, the developmental defects of HELQ-deficient PGCs were alleviated by inhibition of retrotransposition. These results indicate that HELQ maintains the genome stability of PGCs by repressing LINE-1 expression. Our study reveals a critical role of HELQ in PGC development and provides new insights into reproductive disorders caused by defects in DNA damage response factors.
    Keywords:  DNA damage response; HELQ; LINE‐1; primordial germ cells; retrotransposition
    DOI:  https://doi.org/10.1096/fj.202403260R
  7. Biol Reprod. 2025 Jun 25. pii: ioaf139. [Epub ahead of print]
    Oocyte transport against fluid flow to the fertilization site in mice: contributions of cilia beating and peristalsis†.
    Toshiaki Hino.
      The transport of ovulated oocytes to the site of fertilization involves two main processes, the initial collection of the oocyte by the fimbria and its subsequent transport through the upper ampulla. These are crucial events preceding fertilization. Around ovulation, the oviduct exhibits active fluid secretion, peristaltic movements, and ciliary beating, all of which are believed to be involved in oocyte transport. However, their specific contributions require further clarification. In this study, we investigated how these three factors influence oocyte transport to the fertilization site in the oviduct in vivo. The oviduct of anesthetized mice was installed in a fluid-circulating chamber. By introducing fixed and stained cumulus-oocyte complexes (COCs) into the fimbria and injecting a small amount of ink into the oviduct lumen, we monitored oocyte transport and fluid dynamics. Interestingly, while oviduct fluid flowed toward the fimbria, the COC moved in the opposite direction to reach the site of fertilization. Inhibiting ciliary beating disrupted both the collection (or "pickup") and transport of the oocyte, whereas inhibiting peristalsis had no immediate impact on these processes. However, extended inhibition of peristalsis resulted in impaired oocyte transport. Under these conditions, fluid accumulated, and the oviduct lumen expanded, disrupting the intimate contact between the COC and the cilia. These findings indicate that ciliary beating, rather than fluid flow or peristalsis, propels the COC against the fluid flow toward the fertilization site. In addition, peristalsis maintains the luminal conditions required for effective transmission of ciliary propulsion to the COC.
    Keywords:  Ampulla; Cilia; Fluid flow; Fluid production; Infundibulum; Lumina structure; Oocyte transport; Peristalsis
    DOI:  https://doi.org/10.1093/biolre/ioaf139
  8. PLoS Biol. 2025 Jun;23(6): e3003204
    Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.
    Aubrey Converse, Madeline J Perry, Shweta S Dipali, Jose V V Isola, Emmett B Kelly, Joseph M Varberg, Mary B Zelinski, Michael B Stout, Michele T Pritchard, Francesca E Duncan.
      The ovary is one of the first organs to exhibit signs of aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed by macrophage fusion, typically occur in chronic immune pathologies, including infectious and non-infectious granulomas and the foreign body response, but are also observed in the aging ovary. The function and consequence of ovarian MNGCs remain unknown as their biological activity is highly context-dependent, and their large size has limited their isolation and analysis through technologies such as single-cell RNA sequencing. In this study, we define ovarian MNGCs through a deep analysis of their presence across age and species using advanced imaging technologies as well as their unique transcriptome using laser capture microdissection. MNGCs form complex interconnected networks that increase with age in both mouse and nonhuman primate ovaries. MNGCs are characterized by high Gpnmb expression, a putative marker of ovarian and non-ovarian MNGCs. Pathway analysis highlighted functions in apoptotic cell clearance, lipid metabolism, proteolysis, immune processes, and increased oxidative phosphorylation and antioxidant activity. Thus, MNGCs have signatures related to degradative processes, immune function, and high metabolic activity. These processes were enriched in MNGCs compared to primary ovarian macrophages, suggesting discrete functionality. MNGCs express CD4 and colocalize with T-cells, which were enriched in regions of MNGCs, indicative of a close interaction between these immune cell types. These findings implicate MNGCs in modulation of the ovarian immune landscape during aging given their high penetrance and unique molecular signature that supports degradative and immune functions.
    DOI:  https://doi.org/10.1371/journal.pbio.3003204
  9. bioRxiv. 2025 May 03. pii: 2025.04.29.650984. [Epub ahead of print]
    Replication competition drives the selective mtDNA inheritance in Drosophila ovary.
    Cheng Zhang, Zhe Chen, Hansong Ma, Hong Xu.
      Purifying selection that limits the transmission of harmful mitochondrial DNA (mtDNA) mutations has been observed in both human and animal models. Yet the precise mechanism underlying this process remains undefined. Here, we present a highly specific and efficient in situ imaging method capable of visualizing mtDNA variants that differ by only a few nucleotides at single-molecule resolution in Drosophila ovaries. Using this method, we revealed that selection primarily occurs within a narrow developmental window during germline cysts differentiation. At this stage, the proportion of the deleterious mtDNA variant decreases without a reduction in its absolute copy number. Instead, the healthier mtDNA variant replicates more frequently, thereby outcompeting the co-existing deleterious variant. These findings provide direct evidence that mtDNA selection is driven by replication competition rather than active elimination processes, shedding light on a fundamental yet previously unresolved mechanism governing mitochondrial genome transmission.
    DOI:  https://doi.org/10.1101/2025.04.29.650984
  10. Front Endocrinol (Lausanne). 2025 ;16 1595970
    Comprehensive mathematical modeling of age-dependent oocyte quality and quantity for predicting live birth rate.
    Toshio Sujino, Tatsuyuki Ogawa, Akira Komiya, Makiko Tajima, Yuko Takayanagi, Yurie Nako, Hayata Nakajo, Kenichiro Hiraoka, Isao Tamura, Hidetoshi Yamashita, Kiyotaka Kawai.
       Background: Age-related decline in fertility is widely recognized. However, a quantitative evaluation of changes in oocyte quality and quantity remains insufficient. Therefore, developing a mathematical model to quantitatively predict live birth rates affected by these changes is essential for supporting decision-making in assisted reproductive technology.
    Methods: In this retrospective cohort study, we developed a mathematical model to predict live birth rates based on oocyte quality and quantity using IVF treatment data from our clinic over an 8-year period. In the first stage, medically meaningful model functions were selected, and curve fitting was performed using weighted nonlinear least-squares regression to quantify age-related changes in oocyte quality and quantity. For oocyte quality, a comparative analysis was conducted on our clinical data and other large-scale datasets, modeling the live birth rate per single vitrified-warmed blastocyst transfer (SVBT) in correlation with the euploidy rate. For oocyte quantity, the distributions of anti-Müllerian hormone levels, antral follicle count, mature oocyte count, and transferable embryo count were analyzed by two-dimensional weighted nonlinear least-squares regression. In the second stage, logistic regression was applied to analyze live birth rates per SVBT and oocyte pick-up, incorporating multiple explanatory variables.
    Results: The adjusted R-squared values for the curve fitting results were above 0.9, indicating high fitting accuracy. In oocyte quality evaluation, all datasets showed that the values declined to half their peak by the age of 40 years. With respect to oocyte quantity, complete distribution characteristics were successfully modeled, enabling calculations at any percentile value. Logistic regression analysis incorporating blastocyst grade and culture duration as explanatory variables allowed for embryo selection based on a single indicator (i.e., the live birth rate). In the predictive model for live birth rate per oocyte pick-up, which included age, AMH levels, and number of retrieval cycles as explanatory variables, logistic regression analysis showed an AUC of 0.84 and an accuracy of 76.4%, demonstrating high predictive performance.
    Conclusion: Mathematical models of age-dependent oocyte quality and quantity were successfully developed. These models were integrated to construct a multi-variable predictive tool for estimating live birth rates, offering valuable insights for reproductive decision-making.
    Keywords:  anti-Müllerian hormone; curve fitting; fertility decline; live birth rate; mathematical modeling; ovarian aging; prediction
    DOI:  https://doi.org/10.3389/fendo.2025.1595970
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