bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–08–02
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Insufficiency of cohesin regulatory protein PDS5B triggers meiotic failure and aneuploidy in oocytes during advanced maternal aging.
  2. Proprotein convertase activity regulates cumulus-oocyte-complex matrix integrity and cumulus cell migration during ovulation via a GDF9-dependent mechanism.
  3. The maternal KRAB-ZFP ZFPOBI1 reveals structural constraints governing ERV transcriptional co-option in mouse oocytes.
  4. Dual control of PIP2 drives germline/soma segregation in Drosophila.
  5. TRIM37 interacts with TRIM28 to maintain primordial germ cell identity during migration.
  6. Extracellular Zinc Acts as a Dynamic Extracellular Regulator of Fertilization in Xenopus laevis.
  7. Perifollicular stromal cells sustain folliculogenesis via MDK-NCL signaling in mice and humans.
  8. Sperm entry without genome inheritance: incorporate or exclude - egg-intrinsic control of paternal genome fate in Cobitis fish.
  9. Systematic identification of germ granule proteins reveals specialized roles in RNAi and small RNA inheritance.
  10. Nuclear envelope-dependent heterochromatin positioning gates the timing of nucleolar assembly in the early embryo.
  11. Fertility clinics are offering young mitochondria in controversial fertility technique.
  1. Proc Natl Acad Sci U S A. 2026 Aug 04. 123(31): e2605947123
    Insufficiency of cohesin regulatory protein PDS5B triggers meiotic failure and aneuploidy in oocytes during advanced maternal aging.
    Yu Zhang, Jie Bai, Na Li, Bo Xiong.
      Oocytes rely on a cohort of proteins whose sustained expression ensures normal meiotic progression and reproductive competence throughout an animal's reproductive life. Age-related declines in these proteins are a major cause of reduced oocyte quality and female fertility during reproductive aging. Here, we report that the cohesin regulatory protein PDS5B, a dynamically maintained factor in oocytes, declines with age and plays a noncanonical role in the spindle pole formation independent of its cohesion function during oocyte meiotic maturation. Specifically, we found that PDS5B was expressed throughout the oocyte meiosis and localized at the spindle poles at metaphase stages, while its protein abundance was reduced in aged oocytes, concomitant with decreased messenger ribonucleic acid (mRNA) levels and translational efficiency. Knockdown or heterozygous knockout of PDS5B caused spindle assembly defects, meiotic arrest, and aneuploidy in oocytes, ultimately leading to female subfertility. Mechanistically, immunoprecipitation/mass spectrometry analyses revealed that PDS5B recruited deubiquitinating enzyme USP9X to spindle poles to stabilize nuclear mitotic apparatus and promote proper spindle assembly. Moreover, expression of exogenous PDS5B in aged oocytes partially alleviated meiotic defects associated with advanced maternal age. Altogether, our findings uncover a unique spindle pole-specific function of PDS5B in oocytes and suggest that maintaining PDS5B levels may be a potential strategy to improve the quality of aged oocytes.
    Keywords:  NuMA; PDS5B; USP9X; reproductive aging; spindle pole
    DOI:  https://doi.org/10.1073/pnas.2605947123
  2. bioRxiv. 2026 Jul 23. pii: 2026.07.22.738304. [Epub ahead of print]
    Proprotein convertase activity regulates cumulus-oocyte-complex matrix integrity and cumulus cell migration during ovulation via a GDF9-dependent mechanism.
    Caroline E Kratka, Ruixu Huang, Jeffrey Pea, Robin M Skory, Christina D King, Jiyang Zhang, Pawat Pattarawat, Caroline M Milner, Anthony J Day, Nicolas Plachta, Shuo Xiao, Birgit Schilling, Darryl L Russell, Brittany A Goods, Francesca E Duncan.
      Cumulus cells have well-established roles early in ovulation but the key molecules that drive their behavior in later stages, leading to follicle rupture, remain underexplored. Here, we observed that inhibition of proprotein convertases (PCSKs) via a pan-inhibitor (PCI) impaired follicular rupture and disrupted the cumulus matrix integrity within intact follicles. Reduced cumulus cell adherence to the cumulus-oocyte-complex (COC) matrix was also observed in isolated COCs and notably occurred late during the maturation window without affecting oocyte maturation. Visualization of PCSK transcript and protein expression, as well as selective inhibition of specific PCSKs, determined that the observed phenotype in COCs is likely attributed to PCSK5A inhibition. We conducted bulk RNA-sequencing and proteomics of PCI-treated COCs which revealed that PCSK inhibition caused dysregulation of extracellular matrix organization, cell migration/adhesion, and TGF-β signaling pathways. Subsequent validation showed that this inhibition translated to disrupted matrix organization and altered migratory and adhesive behaviors in cumulus cells. The TGF-β ligand GDF9 has a predicted PCSK cleavage site, and supplementation with GDF9 rescued matrix integrity suggesting its role as a downstream substrate of PCSKs to regulate matrix organization. Altogether, this study identified PCSK5A and GDF9 as key regulators of COC matrix integrity and cumulus cell migration during late ovulation. These findings highlight novel factors required for follicle rupture which can be leveraged for the development of fertility therapeutics and contraceptives.
    DOI:  https://doi.org/10.64898/2026.07.22.738304
  3. Front Cell Dev Biol. 2026 ;14 1851851
    The maternal KRAB-ZFP ZFPOBI1 reveals structural constraints governing ERV transcriptional co-option in mouse oocytes.
    Andrina J Stäubli, Yan Huang, Louise J H Rasmussen, Freja Mosegaard Hansen, Hui Mun Loh, Michael J Claxton, Daniel M Messerschmidt.
      Transposable elements (TEs) constitute a major fraction of mammalian genomes and play key roles in gene regulation, particularly during early development. Endogenous retroviruses (ERVs) are highly active in oocytes and early embryos, where their long terminal repeats (LTRs) can act as alternative promoters to generate LTR-initiated transcripts (LITs). Krüppel-associated box zinc finger proteins (KRAB-ZFPs) on the other hand repress TE activity in a sequence-specific manner through recruitment of the co-repressor TRIM28. Here, we identify the mouse KRAB-ZFP ZFPOBI1 as a previously uncharacterized, maternally expressed KRAB-ZFP that selectively targets the RLTR10 LTR subfamilies of the ERVK class. ZFPOBI1 binding is associated with robust TRIM28 recruitment and more modest changes in H3K9me3 enrichment at RLTR10 elements in mouse embryonic stem cells, consistent with canonical KRAB-ZFP-function. In oocytes, we show that RLTR10 elements contribute to LIT formation in a structure-dependent manner. While LTRs serve as transcriptional start sites, efficient splicing into downstream exons predominantly occurs via internal (-int) ERV sequences, indicating a functional separation of transcription initiation and RNA processing. Maternal deletion of ZfpObi1 results in upregulation of a subset of RLTR10-driven LITs, demonstrating a role for ZFPOBI1 in restraining ERV-derived transcription. Notably, full-length RLTR10 elements are subject to additional KRAB-ZFP targeting at internal regions, suggesting that their repression is achieved through multilayered control. Consistent with this, the limited extent of transcriptional deregulation in ZfpObi1-deficient oocytes indicates partial functional redundancy within the KRAB-ZFP family. Together, our findings identify ZFPOBI1 as a regulator of RLTR10 elements and reveal how ERV structural organization constrains both transcriptional co-option and its epigenetic control in the oocyte transcriptome.
    Keywords:  A430033K04Rik; KRAB zinc finger proteins; LTR-initiated transcripts (LITs); RLTR10; TRIM28 (KAP1); endogenous retroviruses (ERVs); oocyte-to-embryo transition; transcriptome
    DOI:  https://doi.org/10.3389/fcell.2026.1851851
  4. Proc Natl Acad Sci U S A. 2026 Aug 04. 123(31): e2604429123
    Dual control of PIP2 drives germline/soma segregation in Drosophila.
    Marcus D Kilwein, Liu Yang, Robert A Marmion, Char A Wynter, Akira Nakamura, Stanislav Y Shvartsman, Elizabeth R Gavis.
      Embryonic cell fate decisions require precise spatial coordination between competing lineage determinants. In the syncytial Drosophila embryo, primordial germ cells (PGCs) and posterior endoderm are specified at the posterior pole in overlapping domains, creating a conflict between germline and somatic fates. PGC formation depends on germ granules, which locally promote production of the phospholipid PIP2 at the posterior plasma membrane. PIP2 regulates actin dynamics leading to membrane protrusions that generate PGCs. We find that the posterior endoderm determinant, the receptor tyrosine kinase (RTK) Torso, antagonizes germ granule activity by activating phosphoinositide 3-kinase (PI3K) which converts PIP2 to PIP3. PIP3 prevents PGC formation, ensuring endoderm specification. Loss of Torso or PI3K expands the posterior PIP2 domain, increasing both the number and spatial extent of PGCs. Germ granules counteract this activity through production of the E3 ubiquitin ligase Germ cell-less (Gcl), which locally eliminates Torso and prevents PI3K-mediated PIP2 depletion at the posterior pole. In gcl mutants, PIP3 accumulates at the posterior membrane and PGC formation fails, a defect that can be partially rescued by targeted posterior expression of the PIP3 phosphatase Pten. Together, these findings demonstrate that mutual antagonism between germ granules and Torso signaling generates a PIP2/PIP3 boundary in the plasma membrane that governs the earliest germline-soma fate decision. Our work reveals how opposing maternal cues can be integrated at the level of membrane phospholipids to pattern cell fate during the earliest stages of development.
    Keywords:  PI3K; PIP3; RTK signaling; endoderm; primordial germ cells
    DOI:  https://doi.org/10.1073/pnas.2604429123
  5. Cell Res. 2026 Jul 30.
    TRIM37 interacts with TRIM28 to maintain primordial germ cell identity during migration.
    Qing Li, Xidi Yin, Chuanyin Li, Li Guo, Yingyi Wang, Yanbo Cheng, Nan Liu, Qi Yin, Yifu Ding, Meng Yan, Zihan Liu, Junyu Chen, Jin Zhang, Shuo Huang, Wangpeng Gu, Anjing Guo, Huanhuan Deng, Yuanyuan Li, Di Chen, Ian Chambers, Hui Zheng, Ronggui Hu, Man Zhang, Jinsong Li.
      During primordial germ cell (PGC) specification, repression of somatic programs is essential for the establishment of germline identity. However, mechanisms that safeguard PGC fate thereafter remain unknown. Here, we identify the E3 ubiquitin ligase TRIM37 as a critical safeguard of PGC fate during migration. Trim37 deficiency causes severe PGC defects beginning at embryonic day 9.5 (E9.5) with complete PGC depletion by E12.5, and leads to an aberrant transition toward somatic cell states. Mechanistically, TRIM37 binds TRIM28 through its MATH domain and ubiquitinates TRIM28 via its RING domain, enhancing the TRIM37-TRIM28 interaction and promoting the nuclear retention of TRIM37. Forced nuclear export of TRIM37 results in PGC loss. Moreover, disruption of TRIM37 ligase activity or mutation of TRIM28 ubiquitination sites compromises PGC maintenance. We further show that the TRIM37-TRIM28 complex, likely acting in cooperation with AP2γ, restricts chromatin accessibility and H3K27ac levels at somatic gene loci, thereby repressing somatic transcriptional programs in PGCs. Together, our findings uncover a TRIM37-TRIM28-AP2γ regulatory complex that safeguards germ cell fate by preventing the activation of somatic transcriptional programs during PGC migration.
    DOI:  https://doi.org/10.1038/s41422-026-01272-2
  6. Biol Reprod. 2026 Jul 31. pii: ioag161. [Epub ahead of print]
    Extracellular Zinc Acts as a Dynamic Extracellular Regulator of Fertilization in Xenopus laevis.
    Rachel E Bainbridge, Kayla M Komondor, Jennifer M Miller, Beatrice L Milnes, Olivia G Brado, Khaalis M T Harris, Paushaly Sau, Eirlys Barbara, Sarah Khanzada, Risha Musuku, Julia Schack, Anne E Carlson.
      For most animals, fertilization of an egg by more than one sperm is embryonically lethal, and eggs therefore deploy multiple blocks to prevent additional sperm from entering an already fertilized egg. While Zn2+ release has emerged as a conserved feature of the slow block, its precise role in external fertilizers remains unclear. Here, we demonstrate that Xenopus laevis fertilization triggers a robust efflux of Zn2+ and that insemination of X. laevis eggs in physiologically relevant concentrations of Zn2+ potently and reversibly suppresses early development. Our findings are consistent with the hypothesis that extracellular Zn2+ inhibits fertilization through multiple mechanisms. Extracellular Zn2+ prevents the fertilization-evoked depolarization, also called the fast block to polyspermy, by acting upstream of the Ca2+-activated Cl- channel TMEM16A. Zn2+ also directly reduces sperm fertilizing capacity, although eggs are significantly more sensitive than sperm. Furthermore, Zn2+ coordinates with the egg's extracellular matrix to stabilize the glycoprotein-rich jelly coat, rendering it resistant to reductive removal and suggesting a structural mechanism by which Zn2+ limits sperm entry. The inhibitory effects of Zn2+ are fully reversed by the extracellular chelator ZX1, reinforcing the conclusion that Zn2+ functions as a dynamic extracellular regulator rather than an intracellular messenger. Our findings establish Zn2+ as a multi-level signal that reinforces fertilization barriers by targeting both gametes and modifying the egg's extracellular environment.
    Keywords:   Xenopus laevis ; Egg activation; Extracellular Matrix; Fertilization; Jelly Coat; Polyspermy block; TMEM16A; Zinc
    DOI:  https://doi.org/10.1093/biolre/ioag161
  7. Cell Discov. 2026 Jul 28. pii: 56. [Epub ahead of print]12(1):
    Perifollicular stromal cells sustain folliculogenesis via MDK-NCL signaling in mice and humans.
    Zhe Zhang, Na Kong, Jie Mei, Xiaoqiang Sheng, Jidong Zhou, Haiquan Wang, Nannan Kang, Yang Zhang, Lina Yu, Pengfei Xu, Xin Zhen, Min Wu, Lijun Ding, Guangyi Cao, Dake Li, Chaojun Li, Guijun Yan, Haixiang Sun.
      Oocyte development requires coordinated metabolic and signaling support from granulosa and theca cells. By performing integrated single-cell RNA sequencing and spatial transcriptomic analyses of murine and human ovaries, we discovered a functionally specialized stromal subtype essential for folliculogenesis. These stromal cells (SCs) with glutamyl aminopeptidase (ENPEP) function, designated perifollicular SCs based on their circumferential follicle localization, exhibit two hallmark features: (1) dynamic proliferation synchronized with follicular maturation from primary to secondary to antral stages, and (2) secretion of midkine (MDK), which activates nucleolin (NCL) receptor signaling to drive granulosa cell (GC) expansion. Furthermore, analyses of ovarian aging revealed the concurrent depletion of perifollicular SCs and the attenuation of MDK-NCL signaling between perifollicular SCs and GCs. The unique spatial confinement and regulatory capacity of perifollicular SCs endow them with the potential to become important components of the follicular functional unit, providing new theoretical support for understanding the molecular regulatory mechanisms of ovarian aging from the perspective of the follicular microenvironment.
    DOI:  https://doi.org/10.1038/s41421-026-00907-3
  8. Genetics. 2026 Jul 29. pii: iyag193. [Epub ahead of print]
    Sperm entry without genome inheritance: incorporate or exclude - egg-intrinsic control of paternal genome fate in Cobitis fish.
    Eleonora Pustovalova, Daniel Kulik, Anatol Marta, Grzegorz Skórzewski, Jan Kotusz, Karel Janko, Katerina Komrskova, Dmitrij Dedukh.
      Fertilization normally ensures the union of maternal and paternal genomes. Yet, some vertebrates reproduce clonally while still requiring sperm to activate the egg, creating a paradox of sperm-dependent but genome-independent development. Here, we provide the first direct in vivo cytological evidence of an early cytoplasmic decision mechanism that distinguishes sperm incorporation from exclusion in gynogenetic vertebrates. Using time-resolved immunofluorescence and spinning-disk confocal microscopy in >1,300 embryos of the Cobitis species complex across sexual, hybrid, and heterogeneric crosses, we detected two reproducible post-fertilization outcomes. Some eggs incorporate the paternal genome and display sperm centrosome licensing, formation of a single microtubule aster, and coordinated chromatin remodelling, including acquisition of activation-associated acetylation marks. In contrast, other eggs exclude the paternal genome and show failure of centrosome licensing, loss of Aurora ABC recruitment, formation of multiple ectopic microtubule asters, and persistent paternal chromatin compaction lacking acetylation. Together, these results indicate that the paternal genome fate is determined by egg-intrinsic mechanisms linking centrosome function with chromatin remodelling.
    Keywords:  fertilization; genome inheritance; gynogenesis; hybridization; paternal genome elimination
    DOI:  https://doi.org/10.1093/genetics/iyag193
  9. Genes Dev. 2026 Jul 31.
    Systematic identification of germ granule proteins reveals specialized roles in RNAi and small RNA inheritance.
    Shihui Chen, Lucas H Prescott, Craig C Mello, Carolyn M Phillips.
      Biomolecular condensates, such as germ granules, organize RNAi pathways critical for fertility and genome regulation. However, the protein composition and functional contributions of these condensates remain poorly defined. Here, we applied TurboID proximity labeling to the Caenorhabditis elegans germ granule protein SIMR-1, integrating mass spectrometry with genetic screening, CRISPR-based tagging, and small RNA sequencing. This systematic approach identified several previously uncharacterized germ granule proteins that contribute to fertility, germline immortality, exogenous RNAi, and transgenerational inheritance. Small RNA sequencing of 21 mutants revealed broad and class-specific defects in siRNA and miRNA biogenesis, with distinct factors associated with defects in WAGO-class 22G-RNAs, CSR-class 22G-RNAs, or histone-directed small RNAs. Among these, we identified PINT-1, a highly disordered protein that directly interacts with and is recruited to germ granules by the PIWI Argonaute PRG-1. PINT-1 is required for piRNA-dependent and -independent secondary siRNA biogenesis and germline development. Comparative genomics revealed that PINT-1 has coevolved with PRG-1 across clade V nematodes, with a conserved structured N terminus and a rapidly diverging repeat-rich intrinsically disordered region. Together, our findings expand the germ granule proteome and reveal how distinct condensate components contribute to specialized functions within the small RNA pathways, while highlighting an evolutionarily coadapted PIWI interactor critical for siRNA biogenesis.
    Keywords:  PIWI; RNA inheritance; RNAi; fertility; germ granule; piRNA pathway
    DOI:  https://doi.org/10.1101/gad.353482.125
  10. bioRxiv. 2026 Jul 22. pii: 2026.07.20.739428. [Epub ahead of print]
    Nuclear envelope-dependent heterochromatin positioning gates the timing of nucleolar assembly in the early embryo.
    Xiangyi Ding, Guanzhi Wang, Daniel Elnatan, Matthew Laurence, Sara Zdanovskis, Megan Couture, Stephanie C Weber, Daniel A Starr, G W Gant Luxton.
      The nucleolus is the largest nuclear condensate, yet how its assembly is developmentally timed remains poorly understood. In the Caenorhabditis elegans embryo, nucleoli normally appear at the 6- to 8-cell stage. Here we show that the LINC complex and nuclear lamina restrain premature nucleolar assembly through heterochromatin organization. Depletion of the embryonic LINC complex proteins SUN-1 or ZYG-12 induces precocious FIB-1-positive nucleoli at the 4-cell stage, particularly in the EMS and P2 blastomeres. LMN-1 depletion produces a more severe phenotype combining premature assembly with impaired disassembly. Loss of the heterochromatin anchor CEC-4 alone has modest effects but strongly suppresses precocious nucleolar assembly caused by LINC complex depletion. LINC complex and lamin perturbations alter the heterogeneity of HPL-2-marked chromatin, and FIB-1 condensates occupy locally HPL-2-depleted regions. These findings identify nuclear envelope-dependent heterochromatin organization as a developmental gate for nucleolar condensate assembly.
    DOI:  https://doi.org/10.64898/2026.07.20.739428
  11. Nature. 2026 Jul 28.
    Fertility clinics are offering young mitochondria in controversial fertility technique.
    Edward Chen.
      
    DOI:  https://doi.org/10.1038/d41586-026-01935-5
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