bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–07–27
seven papers selected by
Gabriele Zaffagnini, Universität zu Köln



  1. Nat Cell Biol. 2025 Jul 22.
      Metabolic regulation is critical in embryonic development and influences key processes such as fertilization, zygotic genome activation, cell compaction, implantation, gastrulation and organ development. Here we explore the interplay between metabolism and embryonic development in the context of important sequential key embryonic events, highlighting the orchestration of developmental processes by various metabolites and signalling molecules. Key metabolites, including glucose, fatty acids and amino acids, act as modulators of developmental processes, while also serving as energy sources and building blocks for cellular structures. Understanding the intricate relationship between metabolism and embryogenesis may provide insights into developmental disorders and potential therapeutic interventions.
    DOI:  https://doi.org/10.1038/s41556-025-01720-y
  2. Biol Reprod. 2025 Jul 24. pii: ioaf165. [Epub ahead of print]
      During mammalian gametogenesis, the chromatin landscape is especially dynamic. Primordial germ cells (PGCs), the precursors to mature male and female gametes, are a transient and small cell population that undergoes profound epigenetic reprogramming. Our knowledge of this process has come primarily from descriptive studies of mouse and human PGCs, and functional studies in mouse. Now, advances in both epigenetic profiling and in vitro gametogenesis are facilitating more in-depth study of germ cell chromatin. Here we review these findings in the broader context of chromatin dynamics in mouse and human PGCs.
    Keywords:  Chromatin; Dna methylation; Epigenetics; Histone modifications; In vitro gametogenesis; Primordial germ cells; Reprogramming
    DOI:  https://doi.org/10.1093/biolre/ioaf165
  3. J Phys Chem Lett. 2025 Jul 23. 7725-7731
      Although understanding the biology of ovarian aging and the timing of menopause is critical for supporting women's reproductive health, many aspects of these processes remain unclear. Stimulated by observations of transitions between different stages of functional units of ovarian units (follicles), a novel stochastic framework has recently been introduced. However, many important aspects of these biological phenomena have been overlooked. In this work, we present a theoretical investigation on synchronization in menopause timing, the role of follicle death, and the temporal dependence of transition rates. Our theoretical method views the depletion in the number of follicles as a multistage stochastic process governed by stage-specific transition and death rates. The narrow distributions of times before menopause are shown to be the result of synchronization when the transition rates between different stages become comparable. We also found that the deaths of the follicles, known as atresia, accelerate the maturation of the follicles. It is suggested that this might be a possible explanation of oversupply when women are born with many more follicles than they need for reproduction. Furthermore, we developed a novel stochastic model of ovarian aging with time-dependent transition rates, and it is shown that this method accounts well for the available data on follicle depletion. Our analysis suggests that there is a specific age at which follicle depletion accelerates. The presented theoretical approach offers novel insights into the mechanisms of complex biological processes, suggesting potential directions for future improvements in women's health.
    DOI:  https://doi.org/10.1021/acs.jpclett.5c01933
  4. FASEB J. 2025 Jul 31. 39(14): e70854
      KIF16B is a member of the kinesin-3 family of motor proteins, which facilitates processes such as vesicle transport, microtubule dynamics, and organelle function during mitosis. In this study, we explored the role of KIF16B in meiosis. Our findings indicate that KIF16B is involved in the meiotic G2-M transition and spindle assembly in oocytes. KIF16B was consistently expressed throughout the meiotic cell cycle of mouse oocytes. After the occurrence of germinal vesicle breakdown, KIF16B became concentrated on microtubules. The exhaustion of KIF16B induced the impairment of meiotic cell cycle progression, which was due to the inactivation of CDK1 and the reduction in the level of cyclin B1, consequently resulting in the failure of germinal vesicle breakdown. Furthermore, aberrant spindle phenotypes and disordered chromosome alignment were observed in KIF16B-depleted oocytes, along with improper kinetochore-microtubule attachments. These abnormal K-MT attachments resulted in the persistent activation of BubR1/Bub3 at the kinetochores. Moreover, KIF16B knockdown destabilized α-tubulin by affecting the activity of histone deacetylase 6 (HDAC6). Further analysis revealed that KIF16B participated in the Ran GTPase-dependent activation of TPX2, which in turn regulated the phosphorylation levels of Aurora A-polo-like kinase 1 (PLK1), driving the proper assembly of the spindle. In conclusion, our data indicated that KIF16B is crucial for meiosis resumption and spindle assembly in mouse oocytes.
    Keywords:  G2/M transition; kinesin; meiosis; oocyte; spindle
    DOI:  https://doi.org/10.1096/fj.202501664R
  5. Gene. 2025 Jul 18. pii: S0378-1119(25)00466-4. [Epub ahead of print] 149677
      The ubiquitin ligase receptor Dora, the Drosophila homolog of ZSWIM8, is a key component of the target-directed microRNA degradation (TDMD) pathway. Previous studies have implicated TDMD - and, consequently, ZSWIM8/Dora - in various developmental processes. Here, we investigate the role Dora plays in Drosophila oogenesis, focusing on ovarian somatic cells. We generated a fly strain with an endogenously tagged Dora protein and observed its presence in both germline and somatic follicular cells of the ovaries. Somatic knockdown of dora revealed its essential role in normal eggshell formation. Specifically, Dora loss led to reduced chorion and vitelline transcript levels and decreased chorion gene amplification, both of which are critical for eggshell protein production. Somatic depletion of Dora reduces the Cut protein levels but did not affect the abundance of other known regulators of eggshell formation, including Ttk69, miR-7 or miR-318 indicating that Dora functions independently of these pathways. Although a direct link between TDMD and chorion eggshell development remains to be confirmed, our findings clearly highlight Dora as a critical regulator in this process. These results pave the way for further investigation into the specific role of TDMD and provide new insights into the regulatory mechanisms underlying animal oogenesis.
    Keywords:  Dora; Drosophila; Local genome amplification; Oogenesis; TDMD; Ttk69; miRNAs
    DOI:  https://doi.org/10.1016/j.gene.2025.149677
  6. Ann Anat. 2025 Jul 18. pii: S0940-9602(25)00326-7. [Epub ahead of print] 152699
      A same set of genes is associated to germline determination and differentiation in almost all Metazoa. Previous studies in several animals, also from distantly related taxa, showed a close association between germline determinants in germ granules and mitochondria, with observations at transmission electron microscopy and immunological approaches. However further investigations are needed to document their respective distribution and elucidate the role of mitochondria in the process of germ granule formation. In the present study we used an emerging animal model to study germline differentiation, Poecilia reticulata, also known as guppy, and different experimental approaches: western blot, immunolocalization, and transmission electron microscopy to investigate the distribution of mitochondria and germ granules during oogenesis. We used anti-Vasa, anti-TDRKH, and anti-TDRD7 to label germline markers, anti-TOMM20 to localize mitochondria, and anti-PLD6 to highlight germline mitochondria. Our observations in previtellogenic oocytes support the co-participation of the nucleus and mitochondria in the production of germ plasm-related material. In previtellogenic oocytes, immunodetection revealed the presence of the germline markers and PLD6 staining in the perinuclear area. The most striking evidence is the observation in the same cell type of plume-shaped structures that at electron microscopy appear as formed by mitochondrial aggregates intermingled with electron-dense germ granules distributed around the nuclear envelope. Overall, our results support the close association between germ granule and mitochondria during germline differentiation, strengthening the foundations for further insights.
    Keywords:  Immunolocalization; PLD6; TDRD7; TDRKH; TEM; TOMM20; Vasa
    DOI:  https://doi.org/10.1016/j.aanat.2025.152699
  7. iScience. 2025 Aug 15. 28(8): 112976
      The zona pellucida, a glycoprotein matrix enveloping the mammalian egg, exerts essential functions during fertilization and early embryonic development. Its safeguard property regulates sperm entry and thus indirectly controls fertility. Limited proteolysis by the metalloproteinase ovastacin, released from the egg during fertilization, induces hardening of the zona pellucida. This precludes sperm entry and protects the embryo until implantation. However, ovastacin leakage before fertilization causes premature hardening and infertility if activity is not inhibited. This highlights the importance of ovastacin regulation by its endogenous inhibitor, fetuin-B. Accordingly, both loss and excessive ovastacin activity are linked to infertility. Here, we review recent discoveries on how ovastacin is precisely controlled to preserve zona pellucida permeability prior to fertilization and prevent penetration afterward. Based on these molecular mechanisms, we propose explanations for clinical phenotypes of recently discovered genetic mutations in ovastacin and discuss how modulation of ovastacin activity might be employed to regulate fertilization.
    Keywords:  Biochemistry; Cell biology; Developmental biology
    DOI:  https://doi.org/10.1016/j.isci.2025.112976