bims-cebooc 2025-09-21 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2025–09–21
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln

Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation.
Mechanisms of human germ cell development.
A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.
Targeted RNAi screen reveals novel regulators of RNA-binding protein phase transitions in Caenorhabditis elegans oocytes.
DNA damage response signaling in oocytes from an oncofertility perspective.
Microfilament-Myosin II Regulates the Differentiation of Multinucleated Cysts into Oocytes and Influences Oocyte Developmental Potential in Mice.
Three types of actomyosin rings within a common cytoplasm exhibit distinct modes of contractility.
Oocyte competence: A systematic review of omics studies and the state of art.
Reprogramming the aging ovarian microenvironment via mitochondrial sharing and structural remodeling.
Transcriptome profiles for defining avian primordial germ cell development.

Nat Commun. 2025 Sep 19. 16(1): 8323

Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation.

Edgar J Soto-Moreno, Nourhan N Ali, Florian Küllmer, Veselin Nasufovic, Michaela Frolikova, Olga Tepla, Jaromir Masata, Dirk Trauner, Amanda A Patterson, Hans-Dieter Arndt, Katerina Komrskova, Magdalena Zernicka-Goetz, David M Glover, Ahmed Z Balboula.

Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, mouse meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar microtubule organizing centers, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identify a previously unrecognized F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrate that F-actin localization on the spindle depends on unconventional myosins X and VIIb. Selective disruption of spindle-localized F-actin, using myosin X/VIIb knockdown oocytes or photoswitchable Optojasp-1, perturbs pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of spindle-localized F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.

DOI: https://doi.org/10.1038/s41467-025-63586-w
Nat Rev Mol Cell Biol. 2025 Sep 16.

Mechanisms of human germ cell development.

Mitinori Saitou, Masahiro Nagano, Ken Mizuta.

Human germ cells are the foundation of human reproduction and development, ensuring heredity and contributing to genetic diversity. Accordingly, their anomalies lead to critical diseases, including infertility. Recent advances in genomics and stem cell-based in vitro gametogenesis research have expanded our knowledge of how human germ cells are specified and differentiate during embryonic and fetal development, elucidating evolutionarily distinctive as well as conserved properties of human germ cell development. Here, based on the evidence from both in vivo and in vitro studies, we provide an integrated review of the progress in our understanding of human embryonic and fetal germ cell development, encompassing germ cell specification, epigenetic reprogramming and sex-specific germ cell development. Knowledge of the mechanisms of human germ cell development will enable its in vitro reconstitution, which in turn will serve as a foundation for innovative medical strategies to prevent germ cell-related diseases, including infertility.

DOI: https://doi.org/10.1038/s41580-025-00893-6
Res Sq. 2025 Sep 03. pii: rs.3.rs-7217416. [Epub ahead of print]

A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.

Siu Sylvia Lee, Sharada Gopal, Amaresh Chaturbedi, Tej Ramachandrula, John OuYang, Rebecca Rodell.

The nuclear hormone receptor NHR-49, a homolog of mammalian PPARα and HNF4α, is a key transcriptional regulator of nutrition sensing and fatty acid metabolism in Caenorhabditis elegans. Here we uncovered a new function of NHR-49 in reproduction - controlling oocyte activation and ovulation. Loss of NHR-49 causes inappropriate oocyte activation and laying of unfertilized oocytes in the absence of sperm, resulting in rapid loss of yolk and stored fat, and drastically shortening of lifespan. We further demonstrated that prevention of yolk transfer into the oocytes largely restore fat storage and partially rescue lifespan in the nhr-49 mutants. Additionally, NHR-49 appears to couple germline proliferation to nutritional status, as evidenced by its requirement for starvation-induced reduction in germline proliferation. Mechanistically, we showed that NHR-49 primarily acts in somatic cells, rather than the germline itself, to regulate oocyte activation and ovulation. We further demonstrated that NHR-49 binds to the promoter of GSA-1 and may stimulate its expression. GSA-1 encodes a G-protein coupled receptor known to act in the gonadal sheath cells to couple sperm sensing and oocyte activation. Our findings therefore suggest a model whereby NHR-49 regulates the expression of GSA-1, which in turn regulates oocyte activation in response to sperm signal. Overall, our findings suggest a mechanistic link between nutrition sensing and fertility and point to regulated retention of reproductive resources to be critical for maintaining longevity.

DOI: https://doi.org/10.21203/rs.3.rs-7217416/v1
bioRxiv. 2025 Sep 08. pii: 2025.09.08.674920. [Epub ahead of print]

Targeted RNAi screen reveals novel regulators of RNA-binding protein phase transitions in Caenorhabditis elegans oocytes.

Mohamed T Elaswad, Grace M Thomas, Corrin Hays, Nicholas J Trombley, Jennifer A Schisa.

The ability of oocytes to maintain their quality is essential for successful reproduction. One critical aspect of oocyte quality and successful embryogenesis after fertilization is the proper regulation of the stores of maternal mRNA by RNA-binding proteins. Many RNA-binding proteins undergo regulated phase transitions during oogenesis, and alterations of the protein phase can disrupt its ability to regulate mRNA stability and translation. In C. elegans , genetic screens have identified regulators of RNA-binding protein condensation in arrested oocytes of females and in embryos, but less attention has focused on phase transitions in maturing oocytes of young adult hermaphrodites. Interestingly, of the relatively few regulators of RNA-binding protein phase transitions identified to date in maturing oocytes, several genes overlap with those required for clearance of protein aggregates in maturing oocytes. To determine the extent to which the temporally linked processes of clearance of damaged proteins and maintenance of RNP complexes are coordinated at a molecular level, we conducted a targeted RNAi screen of genes required for removal of protein aggregates in maturing oocytes. We identified six novel regulators of phase transitions of the KH-domain protein MEX-3 and obtained strong evidence that the regulatory network of protein aggregate clearance overlaps with, but is distinct from, the regulation of MEX-3 phase transitions in the oocyte.

DOI: https://doi.org/10.1101/2025.09.08.674920
Biol Reprod. 2025 Sep 12. pii: ioaf207. [Epub ahead of print]

DNA damage response signaling in oocytes from an oncofertility perspective.

Yunman Sonia Song, Jiyang Zhang, Yingnan Bo, Qiang Zhang, So-Youn Kim, Shuo Xiao.

  The remarkable advances in cancer therapies significantly enhance the survival rates and longevity of cancer patients. Among childhood, adolescent, and young adult female cancer survivors, however, anti-cancer agents frequently cause primary ovarian insufficiency (POI), early menopause, and infertility, primarily due to the depletion of the ovarian reserve. Oocytes, the female germ cells, exhibit a notable susceptibility to DNA damage, given that they remain in meiotic arrest of prophase I for prolonged durations from months to years, which increases the risks of accumulating DNA damage overtime. To counteract this, a tightly controlled DNA damage response (DDR) signaling ensures that only oocytes with an intact genome progress to ovulation, fertilization, and next generations. Chemotherapeutic anti-cancer agents, including doxorubicin, cisplatin, cyclophosphamide, along with irradiation, elicit DNA damage via various mechanisms, including DNA crosslinking, single and double-strand DNA breaks, and oxidative stress. The genotoxic insults activate DDR in the oocytes, which detect and repair DNA damage or initiate apoptosis to eliminate impaired oocytes. Although several protein molecules such as DNA damage-sensing kinases, checkpoint kinases, p53 family transcription factors, and pro-apoptotic molecules, have been discovered, the precise mechanisms of DDR in determining the fate of oocytes, particularly how they differ from those in somatic cells and cancer cells, remain poorly understood. From an oncofertility perspective, the current review analyzes the molecular mechanisms of anti-cancer agent-induced DDR in oocytes and discuss knowledge gaps and urgent future research directions for preserving the ovarian reserve, fertility, and endocrine functions of young female cancer patients.

Keywords:  DNA damage; infertility; oncofertility; oocyte; primary ovarian insufficiency

DOI:  https://doi.org/10.1093/biolre/ioaf207
Adv Sci (Weinh). 2025 Sep 17. e00358

Microfilament-Myosin II Regulates the Differentiation of Multinucleated Cysts into Oocytes and Influences Oocyte Developmental Potential in Mice.

Rui Xu, Menghao Pan, Zhi Zheng, Yaju Tang, Yutong Yan, Sihai Lu, Sha Peng, Baohua Ma.

  Primary oocyte differentiation in females is a complex and selective process; however, its regulatory mechanisms remain poorly understood. In this study, multinucleated cysts are identified as precursors for oocyte differentiation. Disruption of microfilament dynamics disrupts the differentiation of multinucleated cysts into oocytes, resulting in reduced oocyte volume, polarity defects, Balbiani body (B-body) absence, and double-nucleated oocytes. Proteomics analysis reveals that microfilament depolymerization alters the myosin II isoform expression and decreases myosin II activity. Subcellular localization analysis of myosin II in multinucleated cysts demonstrates that myosin IIA co-localized with microfilaments in the cortex and cytoplasm; myosin IIB is associated with the Golgi apparatus; and myosin IIC is distributed diffusely in the cytoplasm. Pharmacological inhibition of myosin II activity or specific knockdown of myosin II isoforms leads to oocyte differentiation abnormalities, including reduced oocyte volume, failed B-body formation, and double-nucleus phenotypes. Compromised differentiation quality of oocytes has long-term consequences, with defective oocytes showing impaired developmental progression, elevated apoptosis, and diminished meiotic competence. These defects are evidenced by reduced rates of germinal vesicle breakdown (GVBD) and first polar body (PB1) excretion, mitochondrial dysfunction, reduced Golgi and endoplasmic reticulum components, and increased spindle abnormalities. In conclusion, this study identifies multinucleated cysts as precursors for oocyte differentiation, highlighting the importance of microfilament myosin II in oocyte differentiation and its long-term influence on oocyte differentiation quality.

Keywords:  mice; microfilament; multinucleated cysts; myosin II; oocyte differentiation

DOI:  https://doi.org/10.1002/advs.202500358
Mol Biol Cell. 2025 Sep 17. mbcE24080373

Three types of actomyosin rings within a common cytoplasm exhibit distinct modes of contractility.

John B Linehan, Alexandra Zampetaki, Michael E Werner, Bryan Heck, Paul S Maddox, Sebastian Fürthauer, Amy S Maddox.

Actomyosin rings are specializations of the non-muscle actomyosin cytoskeleton that drive cell shape changes during division, wound healing, and other events. Contractile rings throughout phylogeny and in a range of cellular contexts are built from conserved components including non-muscle myosin II, actin filaments, and crosslinking proteins. To explore whether diverse actomyosin rings generate contractile force and close via a common mechanism, we studied three instances of ring closure within the continuous cytoplasm of the C. elegans syncytial oogenic germline: mitotic cytokinesis of germline stem cells, apoptosis of meiotic compartments, and cellularization of oocytes. The three ring types exhibited distinct closure kinetics and component protein abundance dyanmics. We formulated a physical model to relate measured closure speed and molecular composition dynamics to ring active stress and viscosity. We conclude that these ring intrinsic factors vary among the ring types. Our model suggests that motor and non-motor crosslinkers' abundance and distribution along filaments are important to recapitulate observed closure dynamics. Thus, our findings suggest that across ring closure contexts, fundamental contractile mechanics are conserved, and the magnitude of contractile force is tuned via regulation of ring component abundance and distribution. These results motivate testable hypotheses about cytoskeletal regulation, architecture, and remodeling. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

DOI: https://doi.org/10.1091/mbc.E24-08-0373
Theriogenology. 2025 Sep 12. pii: S0093-691X(25)00396-6. [Epub ahead of print]249 117670

Oocyte competence: A systematic review of omics studies and the state of art.

Fernanda Amarante Mendes de Oliveira, Gabriela Rodrigues de Paula, Pamela Mara Celestino Soares, Amanda Fonseca Zangirolamo, Fábio Morotti, Anne Kemmer Souza, Fabiana de Andrade Melo-Sterza, Marcelo Marcondes Seneda.

  Competent oocyte is a critical point for successful fertilization and early embryonic development. This systematic review aimed to synthesize scientific evidence from omics studies on oocyte development in cattle during the estrous cycle. Our systematic search followed the PRISMA guidelines, using three databases: PubMed, Scopus, and Web of Science Core Collection. After a critical appraisal of the literature using the Kmet scoring system, ten peer-reviewed articles were included. These studies involved analyses of follicular fluid, cumulus and granulosa cells, oocytes, and maturation media. Transcriptomics predominated among the studies and identified transcriptional patterns associated with oocyte competence in different cell types and stages of the estrous cycle, particularly around the LH surge. In addition, experiments focusing on the ovulatory window as the main theme were identified in the studies. Metabolomic analyses highlighted the role of amino acid turnover and purine metabolism in follicular fluid and maturation media, providing insights into potential biomarkers in oocyte development. The results emphasized the importance of nucleotide metabolism, extracellular matrix interactions, and hormonal signaling pathways, particularly involving genes such as INHBA, TNFAIP6, and TRIB2, in regulating oocyte maturation. This review underscores the power of integrating omics data to elucidate complex molecular mechanisms relevant to the acquisition of oocyte competence. Furthermore, it explores the identification of potential molecular markers that would aid the development of protocols and culture media, while aiming to improve oocyte quality and advance assisted reproductive technologies.

Keywords:  Cattle; Estrous cycle; Metabolomics; Transcriptomics

DOI:  https://doi.org/10.1016/j.theriogenology.2025.117670
Theranostics. 2025 ;15(17): 9279-9293

Reprogramming the aging ovarian microenvironment via mitochondrial sharing and structural remodeling.

Chia-Jung Li, Li-Te Lin, Pei-Hsuan Lin, Jim Jinn-Chyuan Sheu, Zhi-Hong Wen, Kuan-Hao Tsui.

  Rationale: Mitochondrial dysfunction in ovarian granulosa cells (GCs) and cumulus cells (CCs) is a defining feature of reproductive aging, contributing to impaired oocyte quality and reduced fertility. This study investigates whether enhancing cytoskeletal dynamics or promoting structural contact between cells can restore mitochondrial function and mitigate ovarian aging. Methods: Mitochondrial exchange was assessed using co-culture systems, live-cell imaging, and mitochondrial labeling in human ovarian somatic cells. Cytoskeletal modulation was achieved using FTY720, and cell-cell contact was enhanced through soft 3D extracellular matrix (ECM) scaffolds. Functional outcomes were evaluated through ATP assays, mitochondrial membrane potential, Seahorse bioenergetics profiling, and transcriptomic analysis. In vivo validation was conducted in aged mice treated with FTY720. Results: Granulosa and cumulus cells exchanged mitochondria via tunneling nanotubes (TNTs), a process significantly reduced with age. Mitochondrial transfer was contact-dependent and not mediated by paracrine signaling. FTY720 enhanced TNT formation and mitochondrial delivery, restoring ATP levels, membrane potential, and oxidative phosphorylation in aged cells. 3D ECM culture promoted spheroid formation, activated YAP signaling, and improved mitochondrial function without pharmacological agents. In aged mice, FTY720 treatment increased follicle numbers, improved oocyte mitochondrial quality, and elevated serum AMH levels. Conclusions: These findings demonstrate that somatic cell contact is essential for mitochondrial complementation in aging ovaries. By promoting intercellular connectivity through cytoskeletal or microenvironmental remodeling, endogenous mitochondrial sharing can be reactivated to restore bioenergetic function. This approach offers a novel regenerative strategy to counteract reproductive aging.

Keywords:  Cell-cell communication; Mitochondrial transfer; Ovarian aging; Reproductive microenvironment

DOI:  https://doi.org/10.7150/thno.119957
Protein Expr Purif. 2025 Sep 11. pii: S1046-5928(25)00154-8. [Epub ahead of print]237 106812

Transcriptome profiles for defining avian primordial germ cell development.

Kennosuke Ichikawa, Mike J McGrew.

  Avian biology has contributed to many research areas, such as sustainable protein production, endocrinology, developmental biology, neurosciences, and immunology. Primordial germ cells, lineage-restricted stem cells, are key for the conservation of genetic diversity of bird species, as well as for studying germ cell development and producing genetic models to study avian biology. Here, we review the current knowledge of developmental and fate decision processes in avian primordial germ cells focusing on insights revealed by gene expression profiling. We summarized the characteristics and fundamental pathways required for chicken primordial cell growth. In addition, we discuss the common and disparate features of PGCs from chicken compared to other avian species. These insights are valuable for researchers in germ cell biology, reproductive biotechnology, and avian genetic conservation and indicate a need for the analysis of further bird species.

Keywords:  Avian; Chicken; Primordial germ cells; RNA-seq; scRNA-seq

DOI:  https://doi.org/10.1016/j.pep.2025.106812