bims-cebooc 2026-07-12 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–07–12
twenty papers selected by
Gabriele Zaffagnini, Universität zu Köln

Primordial germ cells differentially contribute to the germline in zebrafish.
ER-mitochondria contacts and mitochondrial fusion correlate with increased mitochondrial activity during vertebrate embryogenesis.
Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate.
A barrier to human embryogenesis involves dysregulated 3D genome reprogramming and ZGA collapse.
Cytoplasmic lattices store developmentally poised degradative and cytoskeletal complexes in mammalian eggs.
A variant in human leucine-rich repeat and coiled-coil domain-containing 1 (LRRCC1) elevates meiotic aneuploidy in oocytes.
Single-nucleotide RNA m6A mapping in bovine preimplantation development reveals site-specific regulation of RPL12 at zygotic genome activation.
Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary.
A maternal Polycomb imprint is maintained in early Drosophila development through lower-order methylation states.
ATZ-1 promotes DNA replication efficiency to maintain normal meiotic function.
Modeling human embryo adhesion using a microfluidic platform.
A Three-Dimensional Culture Model Supporting Human Secondary-to-Antral Follicle Development In Vitro.
Visualizing Membrane Nanotube Dynamics in Drosophila Oocyte Using Live-Cell Imaging.
Embryo quality control via lineage-specific aneuploid cell elimination in embryos and stem cell-derived embryo models.
Full-length transcriptomic profiling reveals age-associated isoform remodeling and altered coding potential in the mouse ovary.
The Explosion of Life: Lessons from Live Imaging of Ovulation.
Expression and functional characterization of the TRPV3 channel in domestic cat (Felis catus) mature oocytes.
Expanding the C. elegans toolkit with gonad explants.
Oxytocin-like signaling couples reproductive state to intestinal lipid metabolism in aging C. elegans.
Mitochondrial DNA Inheritance and Germline Purifying Selection: Insights From Drosophila.

Development. 2026 Jul 06. pii: dev.204904. [Epub ahead of print]

Primordial germ cells differentially contribute to the germline in zebrafish.

Maya Pahima, Florence L Marlow.

  Primordial germ cells (PGCs) are the precursors of the germline and among the first cells to be specified during embryogenesis. Contrary to the common assumption that PGCs directly develop into germline stem cells (GSCs), recent data suggest a more complex picture. To functionally examine PGC contributions to the germline, we developed two Cre-based transgenic systems in zebrafish - Germ traCre and Germbow - which provide inducible and indelible germline lineage tracing. Using these systems and known germline markers, we found that PGCs give rise to at least four distinct clone types which are not spatially restricted along the anterior-posterior axis. Moreover, these differential PGC contributions appear to shape lifelong reproductive potential. Examination of clonal contributions to female gamete production revealed that some PGCs give rise to renewing GSCs and others to transient daughters that contribute an early wave of gametes. Collectively, our findings suggest a revised model of vertebrate germline establishment and differentiation potential, with implications for reproductive potential.

Keywords:  Germline; Lineage tracing; Primordial germ cells; Transgenic; Zebrafish

DOI:  https://doi.org/10.1242/dev.204904
Cell Rep. 2026 Jul 09. pii: S2211-1247(26)00693-5. [Epub ahead of print]45(7): 117615

ER-mitochondria contacts and mitochondrial fusion correlate with increased mitochondrial activity during vertebrate embryogenesis.

Anastasia Chugunova, Isabelle Schütz, Hannah Keresztes, Roksolana Kobylinska, Maria Novatchkova, Thomas Lendl, Marcus Strobl, Jörg Fallmann, David Márquez Oller, Michael Schutzbier, Gerhard Dürnberger, Richard Imre, Elisabeth Roitinger, Phylicia Kidd, Pawel Pasierbek, Alberto Moreno Cencerrado, Marlene Brandstetter, Thomas Köcher, Benedikt Agerer, Jakob-Wendelin Genger, Andreas Bergthaler, Andrea Pauli.

  Increased mitochondrial activity is essential for embryo development. Although conserved across organisms, the molecular basis of this increase is unknown, as detailed biochemical analysis in vertebrates is hampered by the limited availability of material. Using zebrafish as a model for vertebrate development, we comprehensively profile mitochondrial activity, morphology, metabolome, proteome, and phospho-proteome, as well as respiratory chain activity. Our data show that the mitochondrial proteome undergoes major changes during embryogenesis. While respiratory chain complex levels remain largely constant, we identify a marked increase in mitochondrial-ER association during early embryogenesis. Moreover, time-lapse imaging of mitochondrial dynamics reveals a transition from fragmented to elongated mitochondria starting during somitogenesis. Overall, our systematic profiling of the molecular and morphological changes of mitochondria during embryogenesis provides a valuable resource for further investigation of mitochondrial function. Our study reveals that increased mitochondrial-ER interaction and changes in mitochondrial morphology may contribute to its regulation during vertebrate development.

Keywords:  CP: cell biology; CP: developmental biology; ER-mitochondrial interaction; metabolism; mitochondria; mitochondrial activation; proteomics; vertebrate embryogenesis; zebrafish

DOI:  https://doi.org/10.1016/j.celrep.2026.117615
Nat Cell Biol. 2026 Jul 10.

Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate.

Chengjie Zhou, Meng Wang, Zhiyuan Chen, Yi Zhang.

Early embryogenesis is accompanied by dynamic epigenetic modifications. Although such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis are less understood. Here, using the dTAG system, we reveal previously underappreciated stage-specific functions of PRC2 in regulating preimplantation and primordial germ cell (PGC) development. We demonstrate that PRC2 plays important roles in regulating maternal-to-zygotic transition and epiblast formation. By systematically analysing H3K27me3 and H3K4me3 dynamics, we redefine the timing of bivalency establishment and uncover a stepwise mechanism governing bivalency acquisition in early embryogenesis. Moreover, PRC2 regulates proper PGC numbers in the epiblast by controlling Esrrb expression in the extraembryonic ectoderm. Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous impact in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-transcription factors networks.

DOI: https://doi.org/10.1038/s41556-026-02002-x
Commun Biol. 2026 Jul 07.

A barrier to human embryogenesis involves dysregulated 3D genome reprogramming and ZGA collapse.

Yuedi Cao, Geng G Tian, Changliang Hou, Shenao Wang, Qing Lu, Shanhe Yu, Meiling Zhang, Yun Sun, Ji Wu.

Early embryonic arrest (EEA) is a critical impediment in assisted reproductive technology, leading to lack of viable embryos. Despite its prevalence, the molecular basis of EEA remains elusive, and the contribution of 3D genome reorganization to this arrest remains largely unexplored. Here, we present an integrated analysis of chromatin architecture and transcriptome dynamics in arrested human embryos during zygotic genome activation (ZGA) stage. Our results reveal extensive chromosomal compartment switching, significant alterations in topologically associating domains (TADs) features, and disrupted chromatin looping in arrested embryos. It suggests that 3D genome reorganization and ZGA failure occur in arrested embryos, marked by reduced abundance of ZGA-critical genes, precocious activation of late-stage developmental pathways, suppression of RNA processing and ribosome biogenesis, and compromised energy metabolism. Additionally, we hypothesize that several transcription factors, including KLF17 and several ZNF family members, serve as regulators in the observed structural or functional changes during developmental arrest. Collectively, our findings suggest that defective 3D genome reprogramming and transcriptomic dysregulation during ZGA are associated with human embryonic arrest at the eight-cell stage. This study advances our understanding of human preimplantation development and its development failures by providing a valuable resource and a conceptual framework for future investigations.

DOI: https://doi.org/10.1038/s42003-026-10614-0
Nat Struct Mol Biol. 2026 Jul 09.

Cytoplasmic lattices store developmentally poised degradative and cytoskeletal complexes in mammalian eggs.

Yujie Li, Wei Zheng, Jiyeon Leem, Chunxiang Wu, Shaogeng Tang, Binyam Mogessie, Yong Xiong.

The cytoplasmic lattice (CPL) in mammalian eggs is essential for early embryonic development but its molecular components, structural organization and functional capacity have remained elusive. Here, using cryo-electron microscopy, we show that the CPL filament in mouse metaphase II eggs contains repeating units with a periodicity of ~37 nm and determine its high-resolution, native structure and complete subunit composition. The CPL architecture organizes maternal-effect proteins, ubiquitination machinery and tubulin into a highly structured reservoir. Maternal-effect proteins form the scaffold of the CPL to sequester a UHRF1-UBE2D3 E3-E2 ubiquitination module and three distinct FBXW-SKP1 E3 ubiquitin ligase components, notably all in activity-excluded states. The CPL further contains αβ-tubulin heterodimers in a GTP-bound state, indicating microtubule-assembly-competent tubulin held in reserve. CPL filaments are capped by a terminal unit that lacks a PADI6 dimer, a scaffold component, suggesting a structural mechanism that prevents further oligomerization. Interactions between neighboring CPL filaments promote the assembly of a three-dimensional network in the egg cytoplasm. Taken together, our work defines how CPL assembly and architecture prime mammalian eggs for ubiquitin-mediated protein degradation and cytoskeletal remodeling during the egg-to-embryo transition.

DOI: https://doi.org/10.1038/s41594-026-01843-2
Res Sq. 2026 Jul 05. pii: rs.3.rs-10131625. [Epub ahead of print]

A variant in human leucine-rich repeat and coiled-coil domain-containing 1 (LRRCC1) elevates meiotic aneuploidy in oocytes.

Marlena Duke, Karen Schindler.

Purpose Globally, infertility rates and the age of women conceiving are both increasing. Aneuploidy is a major cause of early miscarriage, and the incidence of egg aneuploidy increases with maternal age. However, significant variation in age-related aneuploidy rates exists, suggesting that age is not the sole determinant of aneuploid conception risk. We aim to understand what variants in the human genome could predispose a woman to egg aneuploidy at an earlier than average age. Methods The gene encoding human LRRCC1 was fused to Gfp and cloned into an oocyte expression vector designed for in vitro transcription. Site directed mutagenesis was used to create point mutations previously identified in patients with high levels of egg aneuploidy. cRNA was microinjected into mouse oocytes to observe localization, incidence of aneuploidy, and meiotic spindle parameters. Results LRRCC1-Gfp and all variants tested localized to mouse acentrosomal microtubule organizing centers (aMTOC). Expression of the LRRCC1 H69Q variant elevated mouse egg aneuploidy, reduced meiosis I spindle volume and length, caused chromosome misalignment, and reduced aMTOC clustering. Conclusions LRRCC1 promotes centrosome-independent spindle assembly during oocyte meiosis. Human genetic variants in LRRCC1, specifically p.H69Q, alter aMTOC clustering which causes abnormal spindle building, misaligned chromosomes and increased egg aneuploidy.

DOI: https://doi.org/10.21203/rs.3.rs-10131625/v1
Cell Rep. 2026 Jul 06. pii: S2211-1247(26)00713-8. [Epub ahead of print]45(7): 117635

Single-nucleotide RNA m6A mapping in bovine preimplantation development reveals site-specific regulation of RPL12 at zygotic genome activation.

Rajan Iyyappan, Yichi Niu, Yang Li, Hao Ming, Kinga Pajdzik, Noah R Rakestraw, Piyush K Jain, Chuan He, Chenghang Zong, Zongliang Jiang.

  RNA N6-methyladenosine (m6A) is a key regulator of gene expression during early embryogenesis. Using SAC-seq (m6A-selective allyl chemical labeling and sequencing), an antibody-independent m6A profiling method, we generated the first single-nucleotide-resolution m6A map of bovine oocytes and preimplantation embryos. We observed both coordinated and uncoupled relationships between m6A modification and expression of protein-coding and noncoding genes. Integrative analysis of the transcriptome, m6A epitranscriptome, and translatome revealed dynamic m6A remodeling, particularly in ribosomal protein genes. Functional interrogation of a specific m6A site within the RPL12 transcript demonstrated that loss of this modification reduces protein synthesis, disrupts translation-related gene expression, impairs zygotic genome activation, and compromises blastocyst formation. Notably, supplementation with wild-type RPL12 mRNA failed to rescue developmental arrest, suggesting that m6A regulates RPL12 function beyond transcript abundance. Overall, these findings provide a valuable single-nucleotide-resolution resource of m6A dynamics in mammalian embryogenesis and uncover a site-specific mechanism by which m6A regulates translation and developmental competence in early embryos.

Keywords:  CP: Developmental biology; CP: Genomics; RPL12; SAC-seq; ZGA; bovine; m(6)A; preimplantation development

DOI:  https://doi.org/10.1016/j.celrep.2026.117635
Development. 2026 Jul 09. pii: dev.205460. [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.

  The steroid hormone ecdysone controls Drosophila ovarian 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 germ cells, potential direct roles for EcR in the germline 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 their maintenance, 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 EcR functions as a transcriptional repressor in GSCs and cystoblasts to suppress differentiation, but becomes derepressed as ecdysone titer increases and co-repressor expression decreases in dividing germ cell cysts, providing temporal control over germline differentiation. These data support the model that germ cells integrate signals from multiple cell sources that spatially and temporally control their differentiation in response to local and physiological cues.

Keywords:  Ecdysone; Germline stem cell; Oogenesis; Steroid hormone

DOI:  https://doi.org/10.1242/dev.205460
Cell Rep. 2026 Jul 09. pii: S2211-1247(26)00757-6. [Epub ahead of print]45(7): 117679

A maternal Polycomb imprint is maintained in early Drosophila development through lower-order methylation states.

Eleanor A Degen, Natalie Gonzaga-Saavedra, Shelby A Blythe.

  Polycomb group (PcG) proteins regulate embryonic epigenetic states by facilitating mono-, di-, and tri-methylation of H3 lysine 27 (H3K27me1/2/3). For the zygote to inherit a maternal H3K27 methylation state, PcG modifications established during oogenesis must survive until zygotic genome activation. Whether parental PcG states persist through Drosophila embryogenesis remains unclear. Here, we combine stochastic modeling with in vivo experiments to define the fate of maternal H3K27 methylation. We find that the inherited PcG state consists of broad, non-canonical H3K27me2/3 domains and that H3K27me3 is not maintained through cleavage divisions but lost and later re-established within canonical PcG domains. In contrast, H3K27me2 persists in cis on maternal chromatin. Modeling and genetic analyses indicate that this retention is consistent with Polycomb repressive complex 2 (PRC2) allostery-dependent maintenance rather than non-specific, nucleation-independent methylation. These findings suggest that the early embryo inherits a maternal H3K27 landscape that persists primarily as H3K27me2 and is later remodeled into canonical H3K27me3 domains.

Keywords:  CP: genomics; CP: molecular biology; Drosophila; Polycomb; chromatin; embryogenesis; epigenetics

DOI:  https://doi.org/10.1016/j.celrep.2026.117679
FEBS Open Bio. 2026 Jul 09.

ATZ-1 promotes DNA replication efficiency to maintain normal meiotic function.

Taylin E Gourley, Luke W Molesworth, Nethma H Waduge, Fahimeh Eskandari, Peter R Boag, Gregory M Davis.

  Precise coordination of DNA replication and meiotic progression is essential for germline genome stability, yet a complete understanding of this interplay remains unknown. In this study, we show that the absence of Abnormal Transition Zone 1 (atz-1) in Caenorhabditis elegans results in abnormal germline architecture and oocyte development. Specifically, atz-1 mutants display depleted S-phase DNA replication and acute sensitivity to depletion of the checkpoint kinase 1 (chk-1), but not chk-2. These findings suggest that ATZ-1 promotes replication efficiency during premeiotic S-phase, potentially suppressing replication stress and enabling timely meiotic progression. Collectively, this work demonstrates that ATZ-1 contributes to germline genome integrity by influencing cell cycle processes, which, if disrupted, result in numerous downstream germline defects.

Keywords:  DNA replication; cell cycle; germ cells; meiosis; mitosis; oogenesis

DOI:  https://doi.org/10.1002/2211-5463.70300
Sci Adv. 2026 Jul 10. 12(28): eadz2249

Modeling human embryo adhesion using a microfluidic platform.

Sofía Zaragozano, María Pardo-Figuerez, Ana Monteagudo-Sanchez, Anna Quirant, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Jaime Llera-Oyola, Petr Volkov, Sara Maggi, Luis Quintero, Francisco Raga, Pablo Grases, Xavier Santamaria, Inmaculada Moreno, Nicolas Plachta, Carlos Simon, Felipe Vilella.

Embryo adhesion represents a critical step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We validated the model using mouse embryos and human blastocysts, where we showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage reorganization. Moreover, human embryos secreted βhCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity and disorders affecting embryo-endometrium interactions.

DOI: https://doi.org/10.1126/sciadv.adz2249
J Vis Exp. 2026 Jun 16.

A Three-Dimensional Culture Model Supporting Human Secondary-to-Antral Follicle Development In Vitro.

Jianfei Gong, Zhiyun Zhu, Jinze Yang, Jian Han, Mengyuan Tian, Tianren Wang, Haiyan Wang, Huanmin Wang, Jie Yan, Jie Qiao.

Human ovarian folliculogenesis is a complex, tightly regulated process that is challenging to study directly in vivo. Although in vitro models are essential for mechanistic research, existing systems remain suboptimal because they cannot recapitulate the spatiotemporal dynamics of follicle development. This study presents a 3D culture model that supports human follicle development from the secondary to the antral stage. This model successfully recapitulates key in vivo morphological events, including sustained follicular growth, a distinct diameter expansion phase from day 10, and antral cavity formation around day 20. Importantly, this developmental progression culminated in the successful retrieval of viable oocytes at the germinal vesicle (GV) stage. Furthermore, immunofluorescence analysis revealed distinct expression patterns of gonadotropin receptors in somatic cells, consistent with granulosa and theca cell identity. Inner granulosa-like cells exhibited high follicle-stimulating hormone receptor (FSHR), whereas outer theca-like cells showed high luteinizing hormone receptor (LHR) expression. This model offers a valuable platform for studying human folliculogenesis and reproductive toxicology and provides a reference for optimizing in vitro follicle culture systems for secondary-to-antral stage development.

DOI: https://doi.org/10.3791/70713
Bio Protoc. 2026 Jul 05. 16(13): e5278

Visualizing Membrane Nanotube Dynamics in Drosophila Oocyte Using Live-Cell Imaging.

Banhisikha Saha, Sayan Acharjee, Jayeeta Nandi, Mohit Prasad.

  Thin membrane protrusions in cells help them communicate, create traction forces during their movement, and coordinate complex development in multicellular organisms. These structures include cytonemes, tunneling nanotubes, and microtubule-based nanotubes (MT-nanotubes), each with a different cytoskeletal constitution and function. Actin-based cytonemes help deliver signaling molecules, while microtubule-based nanotubes assist with transporting vesicles and organelles. Despite their physiological role, we still do not fully understand how these thin membrane protrusions form and function. In this study, we introduce an improved live-cell imaging method to observe polar cell protrusions during micropyle morphogenesis in developing Drosophila eggs. This technique combines precise developmental staging, careful dissection, and optimized ex vivo culture conditions to maintain tissue health during extended imaging. We also fine-tuned the imaging settings to reduce phototoxicity and thermal stress. This allows for continuous, high-resolution tracking of protrusion dynamics in real time. Our protocol addresses major drawbacks of fixed-tissue methods by capturing the entire process of protrusion formation, extension, and remodeling in intact living tissue. Additionally, it works well with drugs, making it a useful tool for functional studies. Overall, this approach builds a strong foundation for exploring membrane protrusion biology. It can also be applied to investigate similar developmental processes in other systems, aiding our understanding of normal development and diseases. Key features • We optimized a live-imaging protocol ensuring accurate staging and fine dissection of Drosophila egg chambers for reproducible polar cell nanotube visualization. • The enhanced culture conditions maintain egg chamber viability for extended periods, enabling the continuous, real-time observation of dynamic membrane protrusion formation. • The optimized image acquisition settings minimize phototoxicity and sample heating, preventing imaging-induced artifacts and ensuring the acquisition of high-resolution, reproducible datasets while preserving tissue health. • This protocol supports pharmacological treatments for functional perturbation experiments and can be adapted to study similar developmental processes across various other insect systems.

Keywords:  Arthropoda; Drosophila; Germline development; MT-Nanotube; Micropyle; Oogenesis; Polar cells

DOI:  https://doi.org/10.21769/BioProtoc.5728
Nat Commun. 2026 Jul 06.

Embryo quality control via lineage-specific aneuploid cell elimination in embryos and stem cell-derived embryo models.

Lisa K Iwamoto-Stohl, Laura Amaya, Pallavi Panda, Yuqi Wang, Ninadini Sharma, Catherine King, Magdalena Zernicka-Goetz.

Aneuploidy is frequent in human pre-implantation embryos and a leading cause of early pregnancy loss, yet is rarely observed at birth, implying robust embryonic surveillance. Here we define how this surveillance operates after implantation using an integrated, three-lineage stem cell-derived embryo model that recapitulates the epiblast (EPI), visceral endoderm (VE), and extraembryonic ectoderm (ExE). Seeding of aneuploid cells into each lineage independently reveals lineage-specific fates: aneuploid cells are selectively depleted from EPI and VE but persist within ExE. Live imaging captures their removal by apoptosis or physical extrusion. Single-cell RNA sequencing shows p53 activation and Myc repression in aneuploid cells, and pathway perturbations modulate their clearance, confirming causality. Together, these findings demonstrate a post-implantation, lineage-restricted quality-control program that eliminates aneuploid cells from the embryo proper while permitting extraembryonic tolerance. They also establish integrated embryo models as a tractable platform to dissect the molecular logic of developmental quality control.

DOI: https://doi.org/10.1038/s41467-026-75054-0
J Ovarian Res. 2026 Jul 08.

Full-length transcriptomic profiling reveals age-associated isoform remodeling and altered coding potential in the mouse ovary.

Haiyang Wu, Xiaoyu Yin, Min Zhang, Kanghua Zhong, Yalin Liang, Yiduo Wang, Yelian Yan, Xueqi Dong, Yuxin Xu, Hao Yu, Keliang Wu, Shenli Yuan, Chuanxin Zhang.

  Ovarian aging, marked by a progressive diminution of oocyte quality and quantity, is a major contributor to declining female fertility and age-related reproductive disorders. However, transcript-level changes underlying this process remain incompletely understood. In this study, we applied Oxford Nanopore long-read RNA sequencing to profile full-length transcripts from granulosa cells and oocytes of young (6-8 weeks) and aged (10 months) mice, complemented by Illumina short-read sequencing for orthogonal support. We performed transcript annotation, differential expression analysis, alternative polyadenylation (APA) analysis, and weighted gene co-expression network analysis (WGCNA) to investigate age-associated transcriptomic changes. Comprehensive annotation classified 130,730 high-confidence transcripts, including over 100,000 putative novel isoforms, and revealed that aging was associated with a shift toward isoforms with lower predicted coding potential. Exploratory enrichment analysis suggested that transcripts with lower predicted coding potential were associated with biological processes such as protein synthesis and chromosome segregation. APA analysis identified age-associated 3'UTR shortening. Transcript-level differential expression and isoform-switching analysis uncovered 795 significant switching events across both cell types, frequently associated with predicted open reading frame changes and potential protein-domain loss. Exploratory WGCNA highlighted modules associated with aging and cell-type specificity, including an Esr1-derived hub transcript, TALONT000180938, from a gene previously linked to ovarian function and disease. Many disease-associated genes exhibited cell-type-specific isoform usage, with several novel isoforms undetectable at the gene level. Our results indicate that long-read sequencing improves isoform-level resolution of ovarian transcriptomic diversity and identifies candidate aging-associated transcript alterations that may be relevant to reproductive decline.

Keywords:  Full-length transcriptome; Isoform switching; Ovarian aging

DOI:  https://doi.org/10.1186/s13048-026-02193-9
Reproduction. 2026 Jul 08. pii: xaag085. [Epub ahead of print]

The Explosion of Life: Lessons from Live Imaging of Ovulation.

Anita Bichisecchi, Petra Mikec, Christopher Thomas.

  Ovulation is the process by which an egg is released from an ovarian follicle, ready for fertilisation. It is a multi-scale transformation that converts endocrine cues into coordinated tissue and extracellular matrix remodelling, culminating in physical rupture of the follicle wall. Live imaging has reshaped understanding by replacing static snapshots with direct observation of sequence and timing. Here, we outline the architecture of the preovulatory follicle and the LH-driven signalling programmes that coordinate cumulus expansion, oocyte maturation, tissue remodelling and rupture. We then chart key imaging milestones-from early time-lapse of exteriorised ovaries, to clinical endoscopy in humans, perfused ovary preparations, intravital multiphoton microscopy, and ex vivo live imaging of isolated follicles. Finally, we summarise emerging approaches to probe physical regulation, including intrafollicular pressure measurements and complementary methods to quantify tissue and matrix mechanics. Together, these advances show that ovulation is a staged programme that demands quantitative, time-resolved measurements.

Keywords:  Ovulation; ex vivo follicle culture; live imaging; oocyte; ovary

DOI:  https://doi.org/10.1093/reprod/xaag085
Biol Res. 2026 Jul 06.

Expression and functional characterization of the TRPV3 channel in domestic cat (Felis catus) mature oocytes.

Sebastián Vergara, José Duarte-Zúñiga, Claudio Hidalgo, Constanza Suárez-Suárez, Karen Castillo, Matthias Piesche, Felipe Aguilera, Rafael A Fissore, Fernando Hinostroza, Daniel Veraguas-Dávila, Ingrid Carvacho.

   BACKGROUND: Intracellular calcium (Ca2+) signaling is essential for oocyte maturation, activation, and fertilization, with repetitive Ca2+ transients elicited at fertilization being critical for egg activation and early embryonic development. Mouse oocytes express several non-selective cation channels to support these oscillations, including TRPV3, a member of the transient receptor potential (TRP) channel family. In addition to Ca2+, TRPV3 mediates zinc (Zn2+) influx, which is a modulator of cortical granules (CGs) distribution and actin organization. In mammals, CG exocytosis mediates the fertilization-induced block to polyspermy, and pharmacological activation of TRPV3 in mouse oocytes elicits Ca2+ influx sufficient to trigger activation and parthenogenesis. Despite these critical roles in mice, the expression and function of TRPV3 in other mammals remain unexplored. Here, we evaluate the functional expression of TRPV3 channels in cat oocytes.
METHODS: Ovaries from domestic cats were obtained during ovariohysterectomies, and oocytes were isolated and matured in vitro. Trpv3 expression was assessed by RT-PCR from ovaries and germinal vesicle (GV) and metaphase II (MII) oocytes, while TRPV3 localization was evaluated by immunocytochemistry. Mouse WT and TRPV3-knockout oocytes were used as controls for antibody specificity. Functional channel activity was examined using Ca2+ imaging following addition of the TRPV3 agonist 2-APB. Three-dimensional modelling, molecular docking, and comparative sequence analysis of feline, mouse, and human TRPV3 proteins were aligned with MAFFT, focusing on identical and biochemically similar residues within the 2-APB-binding sites as well as pore-forming and temperature-sensing domains to assess potential species-specific functional differences.
RESULTS: We detected Trpv3 transcripts in cat ovaries and in GV and MII oocytes. Immunocytochemistry confirmed TRPV3 protein localization at the oocyte membrane in cats, consistent with reports in mouse oocytes. Additionally, addition of 2-APB elicited robust intracellular increase in Ca2+ in MII cat eggs, demonstrating functional TRPV3 channel activity. Comparative analyses revealed non-conservative substitutions in feline TRPV3 compared to mouse and human TRPV3, particularly within the pore-forming, channel gating, and temperature sensing regions, offering a molecular explanation for species-specific differences in TRPV3 function.
CONCLUSIONS: Our results demonstrate functional TRPV3 expression in domestic cat oocytes. We find distinctive features in feline TRPV3 compared to rodent and human orthologs. These insights support the development of tailored artificial oocyte activation protocols in cats, with potential applications to Assisted Reproductive Technologies (ART) for endangered felids.

Keywords:  2-APB binding sites; Cat oocytes; Oocyte physiology; TRPV3 channel

DOI:  https://doi.org/10.1186/s40659-026-00709-7
Development. 2026 Jul 06. pii: dev.205694. [Epub ahead of print]

Expanding the C. elegans toolkit with gonad explants.

Réda M Zellag, Eric Cheng, Abigail R Gerhold, Jean-Claude Labbé.

  Animal development is a complex process that requires the coordination of a plethora of pathways in space and time. In several species, the availability of tissue explants has provided a simplified context that facilitates mechanistic investigations, particularly into dynamic events. Here, we demonstrate that extruded C. elegans gonads are a viable tissue explant system for this model organism. Using live-cell imaging, we show that C. elegans gonad explants retain many tissue properties that have been documented in vivo, including mitosis, meiosis, apoptosis and gametogenesis. We further show that C. elegans explants are acutely responsive to treatment by the microtubule depolymerizing drug nocodazole. Thus C. elegans gonad explants are a tractable system in which live-cell imaging and acute drug treatment can be combined to decipher the mechanisms governing germline development.

Keywords:   Caenorhabditis elegans ; ex vivo culture; Drug treatment; Gonad development; Tissue explant

DOI:  https://doi.org/10.1242/dev.205694
bioRxiv. 2026 Jul 02. pii: 2026.06.28.735098. [Epub ahead of print]

Oxytocin-like signaling couples reproductive state to intestinal lipid metabolism in aging C. elegans.

Katelyn M Adam, Kathryn M Kuklinski, Charles A Fisher, Will Skinner, Jacqueline Y Lo, Alison Kochersberger, Jennifer L Garrison.

Oxytocin and vasopressin are endogenous bioactive peptides with conserved roles in reproduction and, more recently recognized, in peripheral lipid metabolism. Whether this signaling system also shapes how reproduction declines with age has not been tested in any animal. Here we show that in C. elegans , the oxytocin/vasopressin-like neuropeptide nematocin restrains reproductive output as animals reach mid-life. Nematocin and its two receptors are produced throughout adult life and peak as reproduction begins to wane. Animals lacking receptor signaling produce more offspring in mid-life, an improvement that reflects better egg quality and fertilization rather than improved embryo survival. This benefit is accompanied by changes in intestinal fat metabolism, the worm's equivalent of liver and adipose tissue: nematocin normally limits the activity of a fatty-acid desaturase that is otherwise induced by mating, and it shapes how much yolk reaches developing eggs. The two receptors act through separate routes, one tuning intestinal fat metabolism and the other controlling yolk delivery to the egg. Together, these findings reveal nematocin as a regulator of the intestinal metabolic environment across reproductive age, mirroring the recently described oxytocin-hepatocyte-adipocyte lipid axis in mammals and implicate this conserved signaling system in the coordination of maternal investment during reproductive aging.

DOI: https://doi.org/10.64898/2026.06.28.735098
Annu Rev Genet. 2026 Jul 09.

Mitochondrial DNA Inheritance and Germline Purifying Selection: Insights From Drosophila.

Zhe Chen, Hong Xu.

The mitochondrial genome resides in a highly mutagenic environment and is typically maternally inherited with little recombination, features that should render mitochondrial DNA (mtDNA) prone to the accumulation of deleterious variants. Contrary to this expectation, mtDNA integrity is remarkably well-preserved over evolution. Purifying selection in the female germline that limits transmission of deleterious mtDNA mutations has been documented in various animal models and in humans. Here, we synthesize the literature, with an emphasis on insights from Drosophila, revealing that replication competition-the preferential propagation of healthy genomes over deleterious ones-is the main mechanism driving mtDNA purifying selection in the germline. We highlight developmentally orchestrated mitochondrial processes that couple genome function to replication, enabling selection based on the bioenergetic performance of individual genomes during oogenesis. Finally, we discuss how replication competition can generate genetic conflicts, particularly through the emergence of selfish mtDNA, and how such conflicts may have shaped mtDNA evolution and features of mitochondrial genetics, including maternal inheritance and the mitochondrial bottleneck.

DOI: https://doi.org/10.1146/annurev-genet-011626-033825