bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–01–11
nine papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys, and humans.
  2. Nanos downregulates maternal mRNAs in germline during Drosophila early embryogenesis.
  3. GCL pruning of PIP3 establishes the soma-germline boundary.
  4. Chromosome length is not the sole determinant of sexually dimorphic crossover rates during mammalian meiosis: Insights from genetically diverse mouse strains.
  5. Cross-Species Transcriptomic and Metabolomic Analysis Reveals Conserved and Divergent Fatty Acid Metabolic Regulatory Strategies During Mammalian Oocyte Maturation.
  6. Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary.
  7. Developmentally regulated actin-microtubule cross talk in Drosophila oogenesis.
  8. An insulin receptor activity surge in follicle cells drives vitellogenesis by upregulating CrebA.
  9. Neonatal Mouse Ovary Culture and Whole-mount Follicle Quantification: An Efficient In Vitro Approach for Studying Primordial Follicle Regulation.
  1. Development. 2026 Jan 08. pii: dev.205241. [Epub ahead of print]
    Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys, and humans.
    Baku Nakakita, Ken Mizuta, Yoshitaka Katou, Hidetaka Tasaki, Tomonori Nakamura, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Ikuo Kawamoto, Tomoyuki Tsukiyama, Xun Chen, Guillaume Bourque, Junko Otsuki, Mikiya Nakatsuka, Akihito Horie, Masaki Mandai, Mitinori Saitou, Hiroshi Ohta.
      Understanding the mechanisms for human ovarian folliculogenesis is fundamental to reproductive biology and medicine. Here, we investigated transcriptomic dynamics in individual oocytes and their associated granulosa cells (GCs) during folliculogenesis in mice, monkeys, and humans. Unlike mouse oocytes, which exhibited stage-specific stepwise transcriptomic maturation, monkey and human oocytes showed minimal transcriptomic changes until the secondary follicle stage and could be broadly categorized as either immature or mature. In all three species, most highly variable genes (HVGs) during oocyte growth displayed monotonic up- or down-regulation, with limited overlap in HVGs across species. GCs exhibited similarly species-specific transcriptomic trajectories. Correspondingly, intercellular communication pathways - including ligand-receptor signaling, gap junctions, and metabolic coupling between oocytes and GCs - demonstrated substantial species-specific differences. Nonetheless, X-chromosome dosage compensation and repression of evolutionarily young transposons were conserved across species. We established in vitro culture systems supporting preantral to antral follicle development in monkeys and humans, revealing relatively normal oocyte transcriptome maturation but aberrant GC profiles. By delineating interspecies differences in folliculogenesis, this study provides a framework for understanding human ovarian development and advancing its in vitro reconstruction.
    Keywords:  Cynomolgus monkey; Folliculogenesis; Granulosa cell; Human; Mouse; Oocyte; Transcriptome
    DOI:  https://doi.org/10.1242/dev.205241
  2. Dev Dyn. 2026 Jan 06.
    Nanos downregulates maternal mRNAs in germline during Drosophila early embryogenesis.
    Yasuhiro Kozono, Makoto Hayashi, Miho Asaoka, Satoru Kobayashi.
       BACKGROUND: Many maternal mRNAs in Drosophila primordial germ cells (PGCs) are degraded in concert with the synthesis of new transcripts from the zygotic genome during gastrulation and germ band elongation (3-5 h after egg laying [AEL]). However, few studies have focused on maternal mRNA destabilization in PGCs at the blastoderm stage that is prior to zygotic genome activation (ZGA). Thus, the stability of maternal mRNAs at this stage and regulation of their degradation remain poorly understood. To address this gap, we examined the role of Nanos, an RNA-binding protein known to promote mRNA degradation, in blastoderm-stage PGCs.
    RESULTS: By combining flow cytometry and RNA-sequencing (RNA-seq) analysis of PGCs, we identified the transcripts of 898 genes that were increased in nanos- PGCs. Among them, 298 genes encode maternal transcripts that were downregulated by Nanos in PGCs.
    CONCLUSIONS: Our results show that Nanos downregulates maternal mRNA expression in PGCs before ZGA in Drosophila. As Nanos in C. elegans PGCs has also been reported to promote maternal-to-zygotic transition (MZT) via maternal mRNA downregulation during a transcriptionally silent state, our findings highlight the importance of investigating the function of Nanos for understanding the MZT in PGCs across various animal species.
    Keywords:  Drosophila; germline; maternal‐to‐zygotic transition
    DOI:  https://doi.org/10.1002/dvdy.70107
  3. bioRxiv. 2025 Dec 31. pii: 2025.12.30.697122. [Epub ahead of print]
    GCL pruning of PIP3 establishes the soma-germline boundary.
    Mariyah Saiduddin, Juhee Pae, Asier M Vidal, Marty Alani, Ruth Lehmann.
      Primordial germ cells (PGCs) are the first cells specified in the Drosophila embryo and serve as precursors to the germline. Their formation requires suppression of somatic fates, a process achieved by excluding the receptor tyrosine kinase Torso from the posterior pole through degradation mediated by the ubiquitin ligase adaptor Germ Cell-Less (GCL). Although Torso is known to antagonize PGC formation, the underlying mechanism has remained unclear. Here, we combine optogenetic Ras activation and Ras effector loop mutants to show that Ras signaling suppresses PGC formation independently of the canonical Raf/MEK/ERK pathway. We identify an unexpected early role for Torso in activating phosphoinositide 3-kinase (PI3K), generating posterior membrane domains enriched in phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Elevated PI3K activity disrupts PGC formation, while reduced PI3K activity leads to ectopic PGCs. We further demonstrate that GCL remodels the posterior pole membrane by suppressing Torso-dependent PI3K activation. Clearing PIP3 enables Myosin II enrichment, thereby constricting the pole bud for PGC formation. Together, our findings reveal how antagonistic Torso and GCL activities establish the soma-germline boundary by regulating cortical lipid organization.
    DOI:  https://doi.org/10.64898/2025.12.30.697122
  4. bioRxiv. 2025 Dec 22. pii: 2025.12.19.695521. [Epub ahead of print]
    Chromosome length is not the sole determinant of sexually dimorphic crossover rates during mammalian meiosis: Insights from genetically diverse mouse strains.
    Tegan S Horan, Anna Wood, Stephanie Tanis, Carme Peirau Gabarrell, Paula E Cohen.
      Meiotic recombination generates crossovers (COs), reciprocal exchanges between homologous chromosomes critical for accurate chromosome segregation. Inappropriate CO frequency and distribution drive aneuploidy in human oocytes, with error rates up to 10-fold higher than in sperm despite females exhibiting higher CO frequencies. COs form in the context of the proteinaceous synaptonemal complex (SC) that tethers homologs during prophase I. SC length strongly correlates with CO number, and sexual dimorphism in recombination has long been attributed to longer SCs in females. However, this model is challenged by wild-derived PWD mice in which males consistently generate more COs despite having shorter SCs. Here, we exploit natural genetic variation among inbred mouse strains to dissect the structural and regulatory basis of sexually dimorphic CO regulation. Using cytological markers of SC assembly (SYCP3), recombination progression (RAD51, MSH4), class I CO designation (HEI10, MLH1/MLH3), and chiasmata, we show that SC length is not the sole predictor of CO number. PWD males exhibit stronger CO interference and higher CO number than females, despite reduced SC length. Notably, females show reduced efficiency in designating recombination intermediate to become COs, whereas PWD males display exceptional proficiency. Unexpectedly, although class II COs are rare, they play a disproportionate role in ensuring that every chromosome pair receives at least one CO, thereby safeguarding against aneuploidy. Together, these findings challenge the prevailing view that SC length is the primary determinant of sexually dimorphic CO rates and instead highlight sex-specific regulation of CO designation and pathway usage as key drivers of recombination outcomes.
    DOI:  https://doi.org/10.64898/2025.12.19.695521
  5. Int J Mol Sci. 2025 Dec 30. pii: 397. [Epub ahead of print]27(1):
    Cross-Species Transcriptomic and Metabolomic Analysis Reveals Conserved and Divergent Fatty Acid Metabolic Regulatory Strategies During Mammalian Oocyte Maturation.
    Mostafa Elashry, Yassin Kassim, Bingjie Hu, Hao Sheng, Guangjun Xu, Hagar Elashry, Kun Zhang.
      Mammalian oocyte maturation is a metabolically demanding process relying on lipid metabolism that supplies energy, structural substrates, and signaling mediators. However, a comprehensive cross-species understanding of the dynamic requirement for lipids during this process remains elusive, hindering the optimization of assisted reproductive technologies. Utilizing an integrated single-cell transcriptomic and targeted lipidomic approach, we mapped the metabolic landscape of bovine oocyte maturation. Our analysis uncovered a global transcriptional downregulation, with 3259 genes suppressed during the transition from the germinal vesicle (GV) to the metaphase II (MII) stage. This was particularly apparent in lipid catabolism pathways (e.g., for ACAA1), while mitochondrial energy production genes (ATP6) were upregulated. Lipidomics indicated a selective depletion of saturated fatty acids (SFAs; e.g., C16:0, C18:0) in MII oocytes, while monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) were preferentially retained. Integrated network analysis specified hexadecanoic acid (C16:0) as a central metabolic hub, which rewires its interactions from biosynthetic genes (FASN, ELOVL6) in GV oocytes to degradative enzymes (ACADVL, HADH) in MII oocytes. Expanding to a cross-species transcriptomic atlas, we identified a core set of 59 lipid metabolism genes conserved across bovine, mouse, and human oocytes. Despite this conservation, we discovered stark species-specific regulatory strategies: bovine and human oocytes significantly downregulated fatty acid degradation and elongation post-maturation, whereas murine oocytes maintain pathway activity, upregulating key regulators like Acsl3. Our work unveils an evolutionarily conserved core lipid metabolic program in mammalian oocytes that is adaptively tuned to meet species-specific physiological demands. Bovine and human oocytes prioritize catabolic flexibility, using SFAs for energy, while mouse oocytes maintain their anabolic capacity for membrane biosynthesis. These findings provide a transformative resource for the field, offering biomarkers for oocyte quality and a rationale for enhancing species-tailored lipid formulations to develop in vitro maturation systems and amend reproductive outcomes in both agriculture and medicine.
    Keywords:  lipid; lipidomics; meiosis; metabolomics; oocyte; transcriptomics
    DOI:  https://doi.org/10.3390/ijms27010397
  6. bioRxiv. 2025 Dec 22. pii: 2025.12.19.695538. [Epub ahead of print]
    Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary.
    Lauren E Jung, Alexandria I Warren, Changhong Yin, Weihua Huang, Allison C Simmons, Samantha I McDonald, Lindsay A Swain, Victoria E Garrido, Daniel N Phipps, BiClaireline Cesar, Danielle S Finger, Zhipeng Sun, Todd G Nystul, Elizabeth T Ables.
      In the Drosophila ovary, the steroid hormone ecdysone controls germline stem cell (GSC) maintenance and germ cell differentiation. Prior studies demonstrated that ecdysone regulates germ cell differentiation non-autonomously via the nuclear receptor Ecdysone Receptor (EcR) in ovarian somatic cells. Although EcR is also expressed in GSCs and their differentiating daughters, potential direct roles for EcR in GSCs independent of the soma have not been examined. Here, we demonstrate that EcR functions autonomously in GSCs and cystoblasts to control germline differentiation. While depletion of EcR from GSCs mildly reduces GSC self-renewal, over-expression of EcR specifically in GSCs and cystoblasts impedes germ cell differentiation, phenotypically resembling bag of marbles loss-of-function and Bone Morphogenetic Protein signaling constitutive activation. We propose that while low levels of EcR are essential to maintain GSC self-renewal and permit initial differentiation, higher levels of EcR accumulate in differentiated germ cells to promote transcription of maternal genes, providing temporal control over germline differentiation. These data support the model that stem cells harbor unique mechanisms to integrate signals from multiple cell sources that safeguard their self-renewal in response to local and physiological cues.
    SUMMARY STATEMENT: The nuclear receptor EcR modulates stem cell maintenance and differentiation in ovarian germ cells.
    DOI:  https://doi.org/10.64898/2025.12.19.695538
  7. J Cell Biol. 2026 Mar 02. pii: e202411007. [Epub ahead of print]225(3):
    Developmentally regulated actin-microtubule cross talk in Drosophila oogenesis.
    Wei-Chien Chou, Margot Lakonishok, Wen Lu, Vladimir I Gelfand, Brooke M McCartney.
      Interactions between actin filaments and microtubules (MTs) are essential, but how those mechanisms are orchestrated in complex developing systems is poorly understood. Here we show that actin-MT cross talk regulates actin cable assembly and the assembly and organization of MTs in Drosophila nurse cells during oogenesis. We found that a stable, acetylated MT meshwork develops concurrently with actin cable initiation and requires acetylation for its maintenance. These γ-tubulin-nucleated MTs appear to be cortically tethered via Patronin and Shortstop, extend into the cytoplasm, and coalign with the elongating actin cables. We showed that this MT network is required for actin cable initiation and elongation. We further demonstrated that actin filament assembly via Diaphanous and Enabled promotes cortical tethering of MTs and that loss of the actin filament bundlers Quail/Villin, Singed/Fascin, and Fimbrin resulted in fewer, shorter, and more highly coaligned MTs. Together, our data reveal multiple modes of coordinated actin-MT cross talk that are instrumental for oogenesis.
    DOI:  https://doi.org/10.1083/jcb.202411007
  8. EMBO Rep. 2026 Jan 03.
    An insulin receptor activity surge in follicle cells drives vitellogenesis by upregulating CrebA.
    Xiaoya Wang, Huanju Liu, Zhiyong Yin, Tianning Shao, Lin Li, Jun Ma, Feng He.
      Folliculogenesis is a process that requires accurate interpretation of female physiological cues and elaborate coordination between the growing oocyte and its surrounding follicle cells, each being capable of responding to external signals. Here, we investigate the role of insulin signaling in Drosophila follicle cells. Using a phase separation-based reporter system, we observe a surge of insulin receptor activity in follicle cells during vitellogenic stages, a surge that is disrupted by a maternal high-sucrose diet. Single-cell RNA-seq reveals a diet-sensitive subpopulation of stage-8 follicle cells, which exhibits a reduction in CrebA-mediated transcription of genes for yolk and vitelline membrane proteins. Our results suggest a critical role of CrebA in implementing the stage-specific effect of insulin signaling to boost the secretory capacity of follicle cells. Mechanistically, CrebA is directly repressed by nuclear FoxO that is subject to insulin control, a regulatory axis that we show is conserved in human granulosa cells. This study delineates a mechanism through which insulin and nutrient cues act on a developmental transition via modulating the biosynthetic and secretory functions of the ovary.
    Keywords:  Cyclic-AMP Response Element Binding Transcription Factor; Folliculogenesis; High-Sucrose Diet; Insulin
    DOI:  https://doi.org/10.1038/s44319-025-00672-6
  9. J Vis Exp. 2025 Dec 19.
    Neonatal Mouse Ovary Culture and Whole-mount Follicle Quantification: An Efficient In Vitro Approach for Studying Primordial Follicle Regulation.
    Edgar A Diaz Miranda, Grace Anne Dyer, Faith Wilson, Mariel English, Emma Parry, Taylor VanDeVoorde, Lei Lei.
      In female mammals, primordial follicles form during fetal ovarian development and serve as the sole source for sustaining adult ovarian function. Mechanisms underlying how primordial follicles assemble, maintain dormancy, activate for follicular development, and undergo cell death are important for understanding ovarian physiology and pathological conditions. This study presents a protocol for culturing postnatal mouse ovaries on membrane inserts, an approach that enables the culture and pharmaceutical treatment of intact ovaries for up to 10 days, depending on the developmental stage of the ovary. Changes in the culture conditions can be achieved by transferring inserts containing cultured ovaries between wells on a plate, thereby avoiding physical interference with the tissues during culture. P5 ovaries were isolated and cultured on a 12 mm insert in a 24-well plate as an example. Each ovary was separated within a droplet of DMEM/F12 medium supplemented with 10% FBS, 3 mg/mL BSA, 10 mIU/mL FSH, and Antibiotic-Antimycotic, and gently stabilized on the membrane insert. The medium was changed every two days, and the culture was maintained for a total of five days. Following the culture, ovaries were fixed in 4% paraformaldehyde for 2 h and processed for whole-mount antibody staining of the oocyte marker DDX4. Follicles were staged and quantified based on oocyte size and the nuclear morphology of somatic follicle cells. The results showed that the number of primordial follicles in each ovary was significantly affected by the proper placement of tissues on the membrane insert. In addition, differences in the number of ovaries on each insert may introduce non-biological variations and should be avoided.
    DOI:  https://doi.org/10.3791/69498
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