bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–04–13
sixteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes.
  2. Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.
  3. Reshaping transcription and translation dynamics during the awakening of the zygotic genome.
  4. The chromosomal challenge of human embryos: Mechanisms and fundamentals.
  5. Suppression of oocyte glycine transporter activity in mouse cumulus-oocyte complexes before resumption of meiosis†.
  6. Coordinated regulation of chromatin modifiers reflects organised epigenetic programming in mouse oocytes.
  7. The transcription factor Traffic jam orchestrates the somatic piRNA pathway in Drosophila ovaries.
  8. Bourbon and Mycbp function with Otu to promote Sxl protein expression in the Drosophila female germline.
  9. Germ cell development: Polar granules and PIPs - best buds forever.
  10. Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development.
  11. Single-cell 5-hydroxymethylcytosine landscapes of mouse early embryos at single-base resolution.
  12. Traffic Jam activates the Flamenco piRNA cluster locus and the Piwi pathway to ensure transposon silencing and Drosophila fertility.
  13. DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity.
  14. Musashi-dependent mRNA translational activation is mediated through association with the Scd6/Like-sm family member, LSM14B.
  15. Molecular evidence for pre-chordate origins of ovarian cell types and neuroendocrine control of reproduction.
  16. Structural basis of ZP2-targeted female nonhormonal contraception.
  1. Sci Adv. 2025 Apr 11. 11(15): eadt6159
    The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes.
    Yu Zhang, Jie Bai, Bo Xiong.
      Chromosome cohesion mediated by cohesin complex and its associated proteins is required for accurate chromosome segregation and genomic stability in mitosis. However, because of the distinct operation mechanisms, many proteins might exert different functions during meiosis in germ cells. Here, we document that cohesin-associated protein precocious dissociation of sisters 5A (Pds5A) plays a noncanonical role in the meiotic spindle assembly during oocyte maturation independent of its cohesion function. Pds5A distributes on the spindle fibers in oocytes at both metaphase I and metaphase II stages. Morpholino-based depletion or genetic ablation of Pds5A all lead to defects in spindle organization, chromosome euploidy and meiotic progression in oocytes and thus compromising the female fertility. Mechanistically, Pds5A recruits deubiquitinase ubiquitin-specific protease 14 to the spindle apparatus for stabilization of kinesin family member 5B, regulating the spindle elongation. Collectively, our findings unveil that cohesin-associated protein Pds5A can be used as a spindle regulator during oocyte meiosis.
    DOI:  https://doi.org/10.1126/sciadv.adt6159
  2. Curr Biol. 2025 Apr 04. pii: S0960-9822(25)00315-X. [Epub ahead of print]
    Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.
    Antoine Langeoire, Alison Kem-Seng, Damien Cladière, Katja Wassmann, Eulalie Buffin.
      Chromosome segregation during meiosis is highly error-prone in mammalian oocytes. The mechanisms controlling chromosome attachments and the spindle assembly checkpoint (SAC) have been extensively studied in meiosis I, but our knowledge of these mechanisms during meiosis II is rather limited. Although mammalian oocytes arrest in metaphase II for an extended period awaiting fertilization, some misattached chromosomes may persist. This suggests that the mechanism correcting misattachments is not fully functional during the arrest. In this study, we investigated whether low inter-kinetochore tension, which characterizes incorrect attachments, can be detected by Aurora B/C-dependent error correction in meiosis II. We found that low tension, induced by low dose of STLC in early metaphase II, does indeed mediate microtubule detachment by Aurora B/C and, consequently, anaphase II delay through SAC activation. Surprisingly, we also found that, during prolonged metaphase II arrest, Aurora B/C activity is no longer sufficient to detach low-tension attachments, correlating with high accumulation of PP2A at kinetochores. As a result, the SAC is not activated, and sister chromatids segregate in anaphase II without delay even in the presence of low tension. Hence, during the prolonged metaphase II arrest to await fertilization, oocytes become unable to discriminate between correct and incorrect attachments and may allow errors to persist.
    Keywords:  Aurora B/C; SAC; error correction; meiosis; oocyte; spindle; tension
    DOI:  https://doi.org/10.1016/j.cub.2025.03.030
  3. Curr Opin Genet Dev. 2025 Apr 04. pii: S0959-437X(25)00036-X. [Epub ahead of print]92 102344
    Reshaping transcription and translation dynamics during the awakening of the zygotic genome.
    Louise Maillard, Pierre Bensidoun, Mounia Lagha.
      During the oocyte-to-embryo transition, the transcriptome and proteome are dramatically reshaped. This transition entails a shift from maternally inherited mRNAs to newly synthesized transcripts, produced during the zygotic genome activation (ZGA). Furthermore, a crucial transcription and translation selectivity is required for early embryonic development. Studies across various model organisms have revealed conserved cis- and trans-regulatory mechanisms dictating the regimes by which mRNA and proteins are produced during this critical phase. In this article, we highlight recent technological and conceptual advances that deepen our understanding of how the tuning of both transcription and translation evolves during ZGA.
    DOI:  https://doi.org/10.1016/j.gde.2025.102344
  4. HGG Adv. 2025 Apr 09. pii: S2666-2477(25)00040-5. [Epub ahead of print] 100437
    The chromosomal challenge of human embryos: Mechanisms and fundamentals.
    Anna Ivanova, Elena Korchivaia, Maria Semenova, Igor Lebedev, Ilya Mazunin, Ilya Volodyaev.
      Chromosomal abnormalities in human preimplantation embryos, originating from either meiotic or mitotic errors, present a significant challenge in reproductive biology. Complete aneuploidy is primarily linked to errors during the resumption of meiosis in oocyte maturation, which increase with maternal age, while mosaic aneuploidies result from mitotic errors after fertilization. The biological causes of these abnormalities are increasingly becoming a topic of interest for research groups and clinical specialists. This review explores the intricate processes of meiotic and early mitotic divisions in embryos, shedding light on the mechanisms that lead to changes in chromosome number in daughter cells. Key factors in meiotic division include difficulties in spindle assembly without centrosomes, kinetochore orientation disturbances, and inefficient cell cycle checkpoints. The weakening of cohesion molecules that bind chromosomes, exacerbated by maternal aging, further complicates chromosomal segregation. Mitotic errors in early development are influenced by defects in sperm centrosomes, kinetochore misalignment, and the gradual depletion of maternal regulatory factors. Coupled with the inactive or partially active embryonic genome, this depletion increases the likelihood of chromosomal aberrations. While various theoretical mechanisms for these abnormalities exist, current data remain insufficient to determine their exact contributions. Continued research is essential to unravel these complex processes and improve outcomes in assisted reproductive technologies.
    Keywords:  Chromosomal mosaicism; aneuploidy; cell cycle checkpoints; chromosome segregation errors; kinetochore orientation; meiotic errors; mitotic errors
    DOI:  https://doi.org/10.1016/j.xhgg.2025.100437
  5. Biol Reprod. 2025 Apr 09. pii: ioaf080. [Epub ahead of print]
    Suppression of oocyte glycine transporter activity in mouse cumulus-oocyte complexes before resumption of meiosis†.
    Allison K Tscherner, Jay M Baltz.
      Glycine is a key regulator of cell volume in early preimplantation mouse embryos and supports embryo viability. Its accumulation is initiated when the GLYT1 glycine transporter (SLC6A9) is activated in oocytes at about the same time the oocyte is released from meiotic arrest at the germinal vesicle (GV) stage. The mechanism by which GLYT1 is maintained in an inactive state before ovulation is triggered is unknown. Here, we have shown that GLYT1 activity can remain suppressed in isolated cumulus oocyte complexes (COCs) under defined culture conditions that include keeping COCs physically separated and using the physiological mediator of GV arrest, Natriuretic Peptide Precursor C (NPPC). When GV arrest is instead maintained in oocytes within COCs by inhibiting phosphodiesterase 3A (PDE3A) or cyclin-dependent kinase 1 (CDK1), GLYT1 similarly remains inactive. However, GLYT1 becomes activated in isolated GV oocytes similarly maintained in GV arrest, indicating that cumulus cells are required for suppressing GLYT1 activity. This implied that meiotic arrest was necessary but not sufficient for preventing GLYT1 activation and that an inhibitory factor likely arising from the cumulus was also required. Finally, we found that pyrrophenone, a selective inhibitor of arachidonic acid production by cytoplasmic phospholipase A alpha (cPLAα), caused GLYT1 to become activated in oocytes within COCs despite maintenance of meiotic arrest of the oocyte. Since arachidonic acid levels decrease in oocytes after release from GV arrest, we propose that arachidonic acid may be a candidate for the inhibitory factor in COCs that regulates GLYT1 activity.
    Keywords:  Arachidonic acid; cell volume regulation; cumulus; glycine; meiosis; oocyte
    DOI:  https://doi.org/10.1093/biolre/ioaf080
  6. Epigenetics Chromatin. 2025 Apr 05. 18(1): 19
    Coordinated regulation of chromatin modifiers reflects organised epigenetic programming in mouse oocytes.
    Chloe A Edwards-Lee, Ellen G Jarred, Patrick S Western.
       BACKGROUND: Epigenetic modifications provide mechanisms for influencing gene expression, regulating cell differentiation and maintaining long-term memory of cellular identity and function. As oocytes transmit epigenetic information to offspring, correct establishment of the oocyte epigenome is important for normal offspring development. Oocyte epigenetic programming is highly complex, involving a range of epigenetic modifiers which interact to establish a specific distribution of DNA methylation and histone modifications. Disruptions to oocyte epigenetic programming can alter epigenetic memory and prevent normal developmental outcomes in the next generation. Therefore, it is critical that we further our understanding of the interdependent relationships between various epigenetic modifiers and modifications during oogenesis.
    RESULTS: In this study we investigated the spatial and temporal distribution of a range of epigenetic modifiers and modifications in growing oocytes of primordial to antral follicles. We provide comprehensive immunofluorescent profiles of SETD2, H3K36me3, KDM6A, RBBP7, H3K27me3, DNMT3A and DNMT3L and compare these profiles to our previously published profiles of the Polycomb Repressive Complex 2 components EED, EZH2 and SUZ12 in growing oocytes of wildtype mice. In addition, we examined the nuclear levels and spatial distribution of these epigenetic modifiers and modifications in oocytes that lacked the essential Polycomb Repressive Complex 2 subunit, EED. Notably, histone remodelling in primary-secondary follicle oocytes preceded upregulation of DNMT3A and DNMT3L in secondary-antral follicle oocytes. Moreover, loss of EED and H3K27me3 led to significantly increased levels of the H3K36me3 methyltransferase SETD2 during early-mid oocyte growth, although the average levels of H3K36me3 were unchanged.
    CONCLUSIONS: Overall, these data demonstrate that oocyte epigenetic programming is a highly ordered process, with histone remodelling in early growing oocytes preceding de novo DNA methylation in secondary-antral follicle oocytes. These results indicate that tight temporal and spatial regulation of histone modifiers and modifications is essential to ensure correct establishment of the unique epigenome present in fully grown oocytes. Further understanding of the temporal and spatial relationships between different epigenetic modifications and how they interact is essential for understanding how germline epigenetic programming affects inheritance and offspring development in mammals, including humans.
    Keywords:  DNA methylation; EED; Epigenetic programming; Histone modifications; Maternal germline; Oocytes; PRC2; SETD2
    DOI:  https://doi.org/10.1186/s13072-025-00583-9
  7. Cell Rep. 2025 Apr 06. pii: S2211-1247(25)00224-4. [Epub ahead of print] 115453
    The transcription factor Traffic jam orchestrates the somatic piRNA pathway in Drosophila ovaries.
    Azad Alizada, Aline Martins, Nolwenn Mouniée, Julia V Rodriguez Suarez, Benjamin Bertin, Nathalie Gueguen, Vincent Mirouse, Anna-Maria Papameletiou, Austin J Rivera, Nelson C Lau, Abdou Akkouche, Stéphanie Maupetit-Méhouas, Gregory J Hannon, Benjamin Czech Nicholson, Emilie Brasset.
      The PIWI-interacting RNA (piRNA) pathway is essential for transposable element (TE) silencing in animal gonads. While the transcriptional regulation of piRNA pathway components in germ cells has been documented in mice and flies, their control in somatic cells of Drosophila ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), the Drosophila ortholog of large Maf transcription factors in mammals, is a master regulator of the somatic piRNA pathway. Tj binds to regulatory regions of somatic piRNA factors and the major piRNA cluster flamenco, which carries a Tj-bound enhancer downstream of its promoter. Depletion of Tj in somatic follicle cells causes downregulation of piRNA factors, loss of flamenco expression, and derepression of gypsy-family TEs. We propose that the arms race between the host and TEs led to the co-evolution of promoters in piRNA pathway genes as well as TE regulatory regions, which both rely on a shared transcription factor.
    Keywords:  CP: Developmental biology; CP: Molecular biology; Drosophila; oogenesis; piRNA pathway; transcription factors; transposable elements
    DOI:  https://doi.org/10.1016/j.celrep.2025.115453
  8. Proc Natl Acad Sci U S A. 2025 Apr 15. 122(15): e2426524122
    Bourbon and Mycbp function with Otu to promote Sxl protein expression in the Drosophila female germline.
    Marianne Mercer, Anirban Dasgupta, Krzysztof Pawłowski, Michael Buszczak.
      In Drosophila ovaries, germ cells differentiate through several stages of cyst development before entering meiosis. This early differentiation program depends on both the stepwise deployment of specific regulatory mechanisms and on maintenance of germline sexual identity. The study of female sterile mutations that result in formation of germ cell tumors has been invaluable in identifying the mechanisms that control these developmental events. Here, we characterize the germ cell-enriched gene bourbon (bbn), null mutants of which cause the formation of a mixture of agametic ovarioles and cystic germ cell tumors. We performed proteomic analysis and found Bbn forms a complex with Ovarian tumor (Otu), a protein previously linked with regulation of the sex determination factor Sex lethal (Sxl), and the Drosophila ortholog of c-Myc binding protein (Mycbp). Loss of Mycbp also results in the formation of cystic germ cell tumors. Bbn promotes the stability of Otu and fosters interactions between Otu and Mycbp. Germ cells from bbn and Mycbp mutants display a loss of Sxl expression specifically in the germline. Transgenic rescue experiments show the bbn sterile phenotype is independent from Sxl splicing defects. Further evidence suggests Otu physically interacts with and promotes Sxl protein stability. This function does not depend on Otu's deubiquitinase activity. Last, we find the human orthologs of Otu and Mycbp, OTUD4, and MYCBP, also physically interact, suggesting conservation of function. Together these data provide insights into how a conserved complex promotes the germline expression of Sxl protein and the differentiation of Drosophila germ cells.
    Keywords:  CG14545; Otu; Sxl; germ cell tumor; ovary
    DOI:  https://doi.org/10.1073/pnas.2426524122
  9. Curr Biol. 2025 Apr 07. pii: S0960-9822(25)00271-4. [Epub ahead of print]35(7): R251-R253
    Germ cell development: Polar granules and PIPs - best buds forever.
    Marynelle S Icmat, Julie A Brill.
      Germ granules are specialized RNA-protein condensates that drive germ cell development. A new study reveals that germ granules promote Drosophila germ cell formation by altering membrane mechanics through PIP2 and actin.
    DOI:  https://doi.org/10.1016/j.cub.2025.02.057
  10. Proc Natl Acad Sci U S A. 2025 Apr 15. 122(15): e2410520122
    Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development.
    Sara Formichetti, Joana B Serrano, Urvashi Chitnavis, Agnieszka Sadowska, Na Liu, Ana Boskovic, Matthieu Boulard.
      The main form of intracellular protein glycosylation (O-GlcNAc) is reversible and has been mapped on thousands of cytoplasmic and nuclear proteins, including RNA polymerase II, transcription factors, and chromatin modifiers. The O-GlcNAc modification is catalyzed by a single enzyme known as O-GlcNAc Transferase, that is required for mammalian early development. Yet, neither the regulatory function of protein O-GlcNAcylation in the embryo nor the embryonic O-GlcNAc proteome have been documented. Here, we devised a strategy to enzymatically remove O-GlcNAc from preimplantation embryonic nuclei, where this modification accumulates coincidently with embryonic genome activation (EGA). Unexpectedly, the depletion of nuclear O-GlcNAc to undetectable levels has no impact on EGA, but dampens the transcriptional upregulation of the translational machinery, and triggers a spindle checkpoint response. These molecular alterations were phenotypically associated with a developmental delay starting from early cleavage stages and persisting after embryo implantation, establishing a link between nuclear glycosylation and the pace of embryonic development.
    Keywords:  O-GlcNAc; embryonic genome activation; gene expression; preimplantation development
    DOI:  https://doi.org/10.1073/pnas.2410520122
  11. Cell Rep. 2025 Apr 03. pii: S2211-1247(25)00291-8. [Epub ahead of print]44(4): 115520
    Single-cell 5-hydroxymethylcytosine landscapes of mouse early embryos at single-base resolution.
    Dongsheng Bai, Jinmin Yang, Xiaohui Xue, Yun Gao, Yan Wang, Mengge Cui, Bo He, Hu Zeng, Huifen Xiang, Zijian Guo, Lan Zhu, Juan Gao, Chenxu Zhu, Fuchou Tang, Chengqi Yi.
      DNA methylation and hydroxymethylation are extensively reprogrammed during mammalian early embryogenesis, and studying their regulatory functions requires comprehensive DNA hydroxymethylation maps at base resolution. Here, we develop single-cell 5-hydroxymethylcytosine (5hmC) chemical-assisted C-to-T conversion-enabled sequencing (schmC-CATCH), a method leveraging selective 5hmC labeling for a quantitative, base-resolution, genome-wide landscape of the DNA hydroxymethylome in mouse gametes and preimplantation embryos spanning from the zygote to blastocyst stage. We revealed that, in addition to late zygotic stages, onset of ten-eleven translocation (TET)-mediated DNA hydroxymethylation initiates immediately after fertilization and is characterized by the distinct 5hmC patterns on the parental genomes shaped by TET3 demethylase. We identified persistent clusters of 5hmC hotspots throughout early embryonic stages, which are highly associated with young retroelements. 5hmC is also associated with different regulatory elements, indicating a potential regulatory function during early embryogenesis. Collectively, our work elucidates the dynamics of active DNA demethylation during mouse preimplantation development and provides a valuable resource for functional studies of epigenetic reprogramming in early embryos.
    Keywords:  CP: Developmental biology; CP: Molecular biology; DNA hydroxymethylation; TET3; bisulfite-free method; mammalian early embryo; single cell sequencing
    DOI:  https://doi.org/10.1016/j.celrep.2025.115520
  12. Cell Rep. 2025 Apr 06. pii: S2211-1247(25)00125-1. [Epub ahead of print] 115354
    Traffic Jam activates the Flamenco piRNA cluster locus and the Piwi pathway to ensure transposon silencing and Drosophila fertility.
    Austin J Rivera, Jou-Hsuan Roxie Lee, Shruti Gupta, Linda Yang, Raghuveera Kumar Goel, Joseph Zaia, Nelson C Lau.
      Flamenco (Flam) is a prominent Piwi-interacting RNA (piRNA) locus expressed in Drosophila ovarian follicle cells that silences gypsy/mdg4 transposons to ensure female fertility. Promoter-bashing reporter assays in ovarian somatic sheet (OSS) cells uncover compact enhancer sequences within Flam. We confirm the enhancer sequence relevance in vivo with Drosophila Flam deletion mutants that compromise Flam piRNA levels and female fertility. Proteomic analysis of proteins associated with Flam enhancer sequences discover the transcription factor Traffic Jam (TJ). Tj knockdown in OSS cells causes a decrease in Flam transcripts, Flam piRNAs, and multiple Piwi pathway genes. TJ chromatin immunoprecipitation sequencing (ChIP-seq) analysis confirms TJ binding at enhancer sequences deleted in our distinct Flam mutants. TJ also binds multiple Piwi pathway gene enhancers and long terminal repeats of transposons that decrease in expression after Tj knockdown. TJ plays an integral role in the ongoing arms race between selfish transposons and their suppression by the host Piwi pathway and Flam piRNA locus.
    Keywords:  CP: Molecular biology; Drosophila ovary follicle cell development; piRNA pathway regulation; transcription factors; transposon silencing
    DOI:  https://doi.org/10.1016/j.celrep.2025.115354
  13. Cell Rep. 2025 Apr 08. pii: S2211-1247(25)00315-8. [Epub ahead of print]44(4): 115544
    DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity.
    Lieying Xiao, Hao Jin, Yanna Dang, Panpan Zhao, Shuang Li, Yan Shi, Shaohua Wang, Kun Zhang.
      Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300 during mouse ZGA, we reveal its role in promoting RNA polymerase II (Pol II) pre-configuration at ZGA gene regions and sequentially establishing enhancer activity and regulatory networks. Moreover, p300/CBP-catalyzed acetylation drives Pol II elongation and minor ZGA gene expression by inducing pivotal TFs such as Dux. Remarkably, the supplementation of exogenous Dux rescues ZGA failure and developmental defects caused by the loss of p300/CBP acetylation. DUX functions as a pioneer factor, guiding p300 and Pol II to minor ZGA gene regions and activating them in a manner dependent on the non-catalytic functions of p300/CBP. Together, our findings reveal a mutual dependency between p300/CBP and DUX, highlighting their coordinated role in regulating minor ZGA activation.
    Keywords:  CP: Developmental biology; DUX; RNA polymerase II; ZGA; acetylation; embryo; enhancer; minor ZGA; p300/CBP; preimplantation
    DOI:  https://doi.org/10.1016/j.celrep.2025.115544
  14. Sci Rep. 2025 Apr 10. 15(1): 12363
    Musashi-dependent mRNA translational activation is mediated through association with the Scd6/Like-sm family member, LSM14B.
    Katherine Bronson, Jewel Banik, Juchan Lim, Milla M Reddick, Linda Hardy, Gwen V Childs, Melanie C MacNicol, Angus M MacNicol.
      The Musashi family of sequence-specific RNA binding proteins (Musashi1 and Musashi2) serve a critical role in mediating both physiological and pathological stem cell function in many tissue types by repressing the translation of target mRNAs that encode proteins that promote cell cycle inhibition and cell differentiation. In addition to repression of target mRNAs, we have also identified a role for Musashi proteins in activating the translation of target mRNAs in a context-dependent manner. However, the molecular mechanisms by which Musashi controls target mRNA translational activation have not been fully elucidated. Since Musashi lacks inherent enzymatic activity, its ability to modulate target mRNA translation likely involves recruitment of ancillary proteins to the target mRNA. We have previously identified a number of proteins that specifically associate with Musashi during Xenopus laevis oocyte maturation at a time when Musashi target mRNAs are translationally activated. Here, we demonstrate that one of these proteins, the Scd6/Like-sm family member LSM14B, is a mediator of the Musashi1-dependent mRNA translational activation that is required for oocyte maturation. Unlike previously characterized proteins which interact with the C-terminal domain of Musashi, LSM14B instead associates with the N-terminal RNA recognition motifs. Additionally, we demonstrate that the mammalian Prop1 mRNA, which encodes a key regulator of pituitary development, is translationally activated by Musashi1 in a LSM14B-dependent manner. Our studies support an evolutionarily conserved role for LSM14B in facilitating the ability of Musashi1 to promote target mRNA translation.
    DOI:  https://doi.org/10.1038/s41598-025-97188-9
  15. bioRxiv. 2025 Mar 28. pii: 2025.03.24.644836. [Epub ahead of print]
    Molecular evidence for pre-chordate origins of ovarian cell types and neuroendocrine control of reproduction.
    Periklis Paganos, Carsten Wolff, Danila Voronov, S Zachary Swartz.
      Sexual reproduction in animals requires the development of oocytes, or egg cells. This process, termed oogenesis, requires complex interactions amongst germline and somatic cell types in the ovary. How did these cell types and their signaling interactions evolve? Here we use the sea star Patiria miniata as a non-chordate deuterostome representative to define the ovarian cell type toolkit in echinoderms. Sea stars continuously produce millions of new oocytes throughout their lifespan, making them a practical system to understand the mechanisms that drive oogenesis from a biomedical and evolutionary perspective. We performed scRNA-seq combined with high-resolution 3D-imaging to reveal the ovarian cell types and their spatial organization. Our data support the presence of actively dividing oogonial stem cells and granulosa-like and theca-like cells, which display similarities and possible homology with their mammalian counterparts. Lastly, our data support the existence of an endocrine signaling system between oogonial stem cells and intrinsic ovarian neurons with striking similarities to the vertebrate hypothalamic-pituitary-gonadal axis. Overall, this study provides molecular evidence supporting the possible pre-chordate origins of conserved ovarian cell types, and the presence of an intrinsic neuroendocrine system which potentially controls oogenesis and predates the formation of the hypothalamic-pituitary-gonadal axis in vertebrates.
    DOI:  https://doi.org/10.1101/2025.03.24.644836
  16. Proc Natl Acad Sci U S A. 2025 Apr 15. 122(15): e2426057122
    Structural basis of ZP2-targeted female nonhormonal contraception.
    Elisa Dioguardi, Alena Stsiapanava, Eileen Fahrenkamp, Ling Han, Daniele de Sanctis, José Inzunza, Luca Jovine.
      Monoclonal antibody IE-3 prevents mouse fertilization by binding ZP2, a major component of the oocyte-specific zona pellucida (ZP). We show that an IE-3-derived single-chain variable fragment (scFV) is sufficient for blocking fertilization in vitro and determine the structural basis of IE-3/ZP2 recognition. The high affinity of this interaction depends on induced fit of the epitope, offering insights for nonhormonal contraceptive design without off-target effects.
    Keywords:  X-ray crystallography; ZP2; monoclonal antibody; nonhormonal contraception; zona pellucida
    DOI:  https://doi.org/10.1073/pnas.2426057122
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