bims-cebooc 2026-02-15 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–02–15
eight papers selected by
Gabriele Zaffagnini, Universität zu Köln

MOS is a key regulator of meiotic midbody assembly and prevents abnormal divisions in mouse eggs and their polar bodies.
Somatic gene repression ensures physical segregation of germline and soma in Drosophila embryos.
hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development.
Synthetic germ granules reveal a direct role of Vasa/DDX4 in RNA localization and translational activation.
The dynamic landscape and conserved regulation of the m6Am and m6A methylomes during the human and mouse oocyte-to-embryo transition.
Dilp8 relaxin signaling from ovarian follicle cells to Lgr3+ neurons promotes spontaneous ovulation and oocyte quality in Drosophila.
A decline in follicle cell function is a major driver of Drosophila ovarian aging.
Senescence-Linked Fibrosis in the Aging Human Ovary Revealed by p16-Based Histological Profiling and Spatial Transcriptomics.

J Cell Sci. 2026 Feb 10. pii: jcs.264411. [Epub ahead of print]

MOS is a key regulator of meiotic midbody assembly and prevents abnormal divisions in mouse eggs and their polar bodies.

Gisela Cairo, Muhammad A Haseeb, Zachary Boyce Joy, Karen Schindler, Soni Lacefield.

  Mammalian female meiosis is uniquely regulated to produce a developmentally competent egg capable of supporting embryogenesis. During meiosis I, homologous chromosomes segregate, with half extruded into the first polar body. The egg then arrests at metaphase II and only resumes meiosis and extrudes the second polar body following fertilization. The MOS/MAPK signaling pathway is important for maintaining the metaphase II arrest; in mos-/- mutants, a subset of eggs undergo spontaneous parthenogenetic activation and exhibit additional abnormal cell divisions. To further understand the cell cycle mis-regulation in activated mos-/- eggs, we used time-lapse microscopy to monitor the abnormal divisions. We discovered that, following parthenogenetic activation, the first polar body can assemble a spindle, segregate chromosomes, and divide with timings similar to anaphase II onset in the egg. This behavior contrasts with wildtype polar bodies, which do not divide and typically degenerate. We demonstrate that mos-/- oocytes and polar bodies can exchange cytoplasm for a longer duration due to an extension of telophase I, likely allowing the transfer of cell cycle regulators between the two compartments. Further inspection revealed that mos-/- oocytes have defective meiotic midbody assembly with most oocytes lacking a cap structure, which is needed to separate the oocyte and the polar body prior to abscission. We report that polar bodies of mos-/- eggs can re-enter the cell cycle and undergo additional aberrant divisions. These findings identify MOS as a critical regulator of meiotic midbody formation and uncover a novel consequence of disrupted MOS/MAPK signaling: the potential for polar bodies to become mitotically active.

Keywords:  Abscission; Cytokinesis; MOS; Meiosis; Midbody; Oogenesis; Polar body

DOI:  https://doi.org/10.1242/jcs.264411
EMBO Rep. 2026 Feb 09.

Somatic gene repression ensures physical segregation of germline and soma in Drosophila embryos.

Miho Asaoka, Mizuki Kayama, Tomoki Kawagoe, Makoto Hayashi, Shumpei Morita, Satoru Kobayashi.

  In many animals, primordial germ cells are transiently segregated outside the somatic-cell cluster that forms the embryo's body during early embryogenesis. This physical segregation of the germline from the soma has long been believed to be crucial for germline development, but the mechanisms controlling this segregation and its developmental significance remain unclear. Here, in Drosophila, we show that somatic gene silencing in the germline is essential for maintaining this segregation. Primordial germ cells (pole cells) lacking the Nanos- and Polar granule component (Pgc)-dependent dual repression mechanism misexpress widespread somatic genes. They form abnormal cellular protrusions, invade adjacent somatic epithelium, and intermingle with somatic cells. These mislocalized pole cells ultimately undergo cell death, whereas properly segregated cells survive. Notably, knockdown of miranda (mira), one of the somatic genes ectopically expressed, rescues these phenotypes. Our findings uncover a previously unrecognized mechanism whereby somatic gene silencing safeguards the physical boundary between the germline and the somatic cells forming the embryo's body, highlighting its potential role in ensuring germline viability during early development.

Keywords:   Drosophila ; Apoptosis; Germ Cell; Germ-soma Segregation; Nanos

DOI:  https://doi.org/10.1038/s44319-026-00710-x
Nat Commun. 2026 Feb 12.

hnRNPM cooperates with BCAS2 to modulate alternative splicing during oocyte development.

Shumin Zhou, Dalin Liu, Shiming Gan, Ziqi Yu, Ruibao Su, Hao Zhou, Jiaqi Zhang, Haoran Xu, Yifan Zhao, Hua Zhang, Zuoqi Deng, Xuan Wu, Chunhai Luo, Yunlong Liu, Shuiqiao Yuan, Heng-Yu Fan, Fei Sun.

Growing oocytes accumulate maternal mRNA to support subsequent meiotic maturation and maternal-to-zygotic transition. However, the regulatory mechanisms governing the fate of these maternal mRNAs remain largely unknown. Here, we identified heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a critical regulator of pre-mRNA alternative splicing during mouse oocyte development. Genetic ablation of hnRNPM leads to severe cytoplasmic defects, meiotic arrest, and complete female infertility. Using SCAN-seq, we uncovered novel transcript isoforms and systematically characterized hnRNPM-regulated alternative splicing events. Furthermore, LACE-seq revealed hnRNPM-binding sites at single-nucleotide resolution in oocytes, linking its RNA-binding activity to splicing fidelity. Additionally, hnRNPM interacts with BCAS2, a known splicing factor critical for oocyte development, and modulates its binding to pre-mRNA loci to precisely control the alternative splicing. Overall, our study not only uncover an essential role of hnRNPM in mammalian oocyte development and female fertility but also unveils a critical regulatory network governing alternative splicing during oocyte development.

DOI: https://doi.org/10.1038/s41467-026-69176-8
bioRxiv. 2026 Feb 03. pii: 2026.02.01.703065. [Epub ahead of print]

Synthetic germ granules reveal a direct role of Vasa/DDX4 in RNA localization and translational activation.

Ruoyu Chen, Henoc Zinga, Jay S Goodman, Ruth Lehmann.

Cytoplasmic RNA granules, including stress granules, P bodies, neuronal RNA granules, and germ granules, are essential for RNA storage and regulation across a wide range of organisms. However, dissecting the contributions of individual factors to granule function is challenging because of the interdependence of components in vivo . This is especially true for DEAD-box helicases, common regulators of mRNA granules, whose specific contributions remain unclear. In this study, we developed a synthetic approach to de novo generate germ granules, enabling us to identify the minimal machinery needed for RNA localization and translational activation. Using a self-assembling PopTag-based scaffold derived from Caulobacter fused to the RNA-binding domain (RBD) of the germplasm organizer Oskar, we found that the recruitment of endogenous germ granule mRNAs ( nanos and pgc ) depended on the DDX4 protein Vasa. By employing orthogonal RNA tethering approaches, we demonstrate that Vasa is both necessary and sufficient for localized mRNA translation. Consistent with these findings, acute depletion of Vasa from endogenous germ granules specifically reduced Nanos translation without affecting mRNA localization, confirming Vasa as a core factor linking RNA recruitment to localized translational activation. These in vivo reconstitution experiments reveal a two-component module in which a scaffold RBD and the Vasa helicase, but not other DEAD-box helicases, enable RNP condensates to accumulate specific RNAs and promote their translation. Overall, our study uncovers previously unrecognized functions of an RNA helicase within ribonucleoprotein condensates and demonstrates the power of synthetic biology to analyze complex biomolecular condensates in living organisms.

DOI: https://doi.org/10.64898/2026.02.01.703065
Nucleic Acids Res. 2026 Feb 05. pii: gkag103. [Epub ahead of print]54(4):

The dynamic landscape and conserved regulation of the m6Am and m6A methylomes during the human and mouse oocyte-to-embryo transition.

Ruibao Su, Zongchang Du, Sen Li, Hanyan Liu, Di Gao, Shaoquan Zhan, Chao Li, Tie-Gang Meng, Lei-Ning Chen, Li-Hua Fan, Yanbin Dong, Shuai Jiang, Zhong Guo, Lei Li, Shi-Ming Luo, Qing-Yuan Sun, Xiang-Hong Ou.

N 6-methyladenosine (m6A) and N6, 2'-O-dimethyladenosine (m6Am) are two RNA modifications that play essential roles in diverse RNA metabolic processes and functions. Despite their importance, the dynamic landscapes and regulatory patterns of m6A and m6Am during the oocyte-to-embryo transition (OET) in humans and mice remain elusive. Here, we developed a highly sensitive method, MeLACE-seq, to profile the m6A and m6Am landscapes across human and mouse oocytes to pre-implantation embryos. We reveal that the zygotic genome activation (ZGA) stage serves as a regulatory node where both the m6A and m6Am methylomes undergo dramatic, species-specific changes. Moreover, transcripts marked by m6A and m6Am are generally expressed and translated at higher levels than unmarked transcripts. Additionally, we discovered that m6A modifications are extensively deposited on human retrotransposon RNAs. These m6A marks exhibit a functional shift, showing a positive correlation with elevated retrotransposon RNA levels in pre-ZGA embryos, but a negative correlation with their expression around the ZGA stage. Together, these findings reveal conserved and species-specific regulatory patterns of the epitranscriptome during human and mouse OETs, providing new insights into the roles of RNA modifications in embryogenesis.

DOI: https://doi.org/10.1093/nar/gkag103
Development. 2026 Feb 09. pii: dev.204955. [Epub ahead of print]

Dilp8 relaxin signaling from ovarian follicle cells to Lgr3+ neurons promotes spontaneous ovulation and oocyte quality in Drosophila.

Yanel Volonté, Fabiana Heredia, Rebeca Zanini, Juliane Menezes, María Sol Perez, Mafalda Gualdino, Lara Lage, Leonor da Silva Luz, Andreia P Casimiro, Catarina C F Homem, Maria Luísa Vasconcelos, Andres Garelli, Alisson M Gontijo.

  Ovulation enables mature oocytes to exit the ovary for potential fertilization. In Drosophila, ovulation is induced by mating but also occurs spontaneously in virgins, with rates varying widely in natural populations: short oocyte retention is ancestral, while longer retention is favored in colder climates. The molecular regulation of spontaneous ovulation remains unclear. Here, we show that disrupting the relaxin/insulin-like peptide Dilp8 or its receptor Lgr3-an orthologue of vertebrate RXFP1/2-in follicle cells or specific neurons, respectively, delays ovulation, slows average egg transit time in the reproductive tract, and facilitates oogenesis progression beyond ∼2 mature oocytes per ovariole, leading to mature follicle accumulation in the ovary. Mating largely rescues these defects, suggesting the pathway is dispensable post-mating. Dilp8-Lgr3 signaling ensures high oocyte quality by promoting elimination of lower-quality aging oocytes and by antagonizing oogenesis progression via an undefined mechanism downstream of Lgr3+ neurons. Our findings provide a molecular basis for oocyte retention time regulation in Drosophila involving ovarian-nervous system cross-talk, and bring further support for an ancient, conserved role for relaxin-like signaling in regulating ovulation and overall female reproductive physiology.

Keywords:  Dilp3; Fecundity; G-protein coupled receptor; Insulin-like peptide; Reproductive tract; Vitellogenesis checkpoint

DOI:  https://doi.org/10.1242/dev.204955
bioRxiv. 2026 Feb 08. pii: 2026.02.05.704044. [Epub ahead of print]

A decline in follicle cell function is a major driver of Drosophila ovarian aging.

Emily Allyson Wolfgram, Todd Gregory Nystul.

The ovary is one of the first organs to lose functionality with age. We found that aging of the Drosophila ovary is characterized by an accumulation of phenotypes in the somatic compartment, including failure of the follicle cells to encapsulate germ-cell cysts, an extended S phase, and increased DNA damage. In aged ovaries, follicle encapsulation defects are associated with the lack of a germ-cell cyst checkpoint in early oogenesis. Single-cell RNA sequencing revealed that, across all cell types in the ovary, cells in the follicle lineage have the highest number of differentially expressed genes. Overexpression of Atg8a, a key autophagy machinery gene homologous to mammalian LC3, specifically in follicle cells prevents age-associated decline in the follicle epithelium and loss of reproductive capacity. Collectively, these findings demonstrate that genetic manipulation of a small population of ovarian somatic cells is sufficient to improve both cell-autonomous and non-autonomous features of reproductive aging.

DOI: https://doi.org/10.64898/2026.02.05.704044
Res Sq. 2026 Feb 06. pii: rs.3.rs-8290960. [Epub ahead of print]

Senescence-Linked Fibrosis in the Aging Human Ovary Revealed by p16-Based Histological Profiling and Spatial Transcriptomics.

Birgit Schilling, Mark Watson, Pooja Devrukhkar, Natalia Murad, Fan Wu, Moo Joong Kim, Hannah Anvari, Uyen Tran, Nicolas Martin, Tommy Tran, Giuliana Zaza, Kevin Schneider, Bikem Soygur Kaya, Elisheva Shanes, Denis Wirtz, MaryEllen Pavone, Simon Melov, Pei Hsun Wu, David Furman, Francesca Duncan.

Cellular senescence is implicated as a driver of ovarian aging, but senescent cells in the human postmenopausal ovary remain poorly defined. Using spatially resolved p16INK4a protein expression, a canonical senescence marker, we identified and mapped senescent cells in postmenopausal ovaries. We integrated p16 immunohistochemistry, multiplexed immunofluorescence, spatial transcriptomics, and AI-guided digital pathology to map senescent microenvironments. p16-positive cells formed discrete stromal, vascular, and cyst-associated clusters that increased with age and were enriched for macrophages and myofibroblast-like cells. Whole-transcriptome profiling of 92 spatial regions uncovered a 32-gene p16-associated signature, BuckSenOvary, that distinguished p16-positive regions across cortex and medulla. BuckSenOvary is characterized by suppression of cell-cycle regulators and activation of inflammatory and extracellular-matrix remodelling genes. AI-based collagen matrix analysis confirmed that p16-positive regions exhibit more architecturally complex collagen, demonstrating that focal senescent microenvironments are fibro-inflammatory. These findings position senescent ovarian niches as therapeutic targets to preserve ovarian function.

DOI: https://doi.org/10.21203/rs.3.rs-8290960/v1