bims-cebooc 2026-07-19 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–07–19
eighteen papers selected by
Gabriele Zaffagnini, Universität zu Köln

Live imaging captures the events immediately following fertilization.
Reply: Stem cell-based embryo models: scientific promise clashes with ethical reality.
Oocyte Kinetochores at the Nexus of Meiotic Drive and Segregation Fidelity.
Chromosome Architecture Defined by the Meiosis-Specific Cohesin in Mammalian Germ Cells.
High-resolution global recombination mapping in C. elegans reveals sexual dimorphisms shaped by meiotic chromosomal features and structures.
Single-molecule m 6 A profiling reveals position-dependent mRNA regulation and non-canonical roles for Ythdf2 in early embryogenesis.
Histone Modifications in Mammalian Early Embryos.
Contribution of cohesins STAG1 and STAG2 to preimplantation development in mice.
The microprotein Dafcin resembles influenza HA fusion peptide and regulates the size of storage lysosomes in the germline.
A workflow for Live Imaging and Quantitative Analysis of Acentrosomal Microtubule Networks in Drosophila Oocytes.
Asymmetric Chromosome Establishment and Segregation During Germline Stem Cell Division.
Landscape of parental postzygotic mutations across >11,000 rare disease trios.
Satellite DNA sequence dictates pericentromere heterochromatin formation and function.
Recent Progress in Characterizing Germline Mutations and Their Transmission Across Generations.
Metabolic imaging for gamete and embryo assessment through advanced microscopy technologies: a novel avenue for artificial intelligence?
Nucleoskeletal Proteins in Early Embryogenesis.
Spaceflight multi-omics reveals vulnerabilities of human germ cell development.
Advances in bovine oocyte in vitro maturation: mechanisms and strategies.

Dev Cell. 2026 Jul 17. pii: S1534-5807(26)00239-X. [Epub ahead of print]

Live imaging captures the events immediately following fertilization.

Robin M Skory, Ana Domingo-Muelas, Sarah Declercq, Winter Vandenberghe, Piotr Tetlak, Blake Hernandez, Dominic Stoop, Colin C Conine, Maté Biro, Björn Heindryckx, Nicolas Plachta.

  Fertilization involves dynamic sperm-egg interactions, yet has been primarily studied in static samples. Here, we use high-resolution live imaging to capture fertilization from the moment of sperm binding in zona-intact mouse oocytes. We identify two phases of sperm remodeling: a static phase, during which sperm remain beneath the oocyte cortex as DNA decondensation and histone loading occur, and a mobile phase characterized by stereotyped sperm movement. Initial displacement away from the spindle is driven by cytoplasmic streaming, with manipulations in mouse indicating that sperm movement requires chromatin decondensation and oocyte polarization. Subsequently, polar body cytokinesis generates convergent cortical flows that draw sperm toward the emerging female pronucleus. Finally, we capture sperm-egg fusion in human oocytes and characterize post-fusion events including meiotic resumption and sperm movement, offering a live-imaging description of human fertilization dynamics. Together, these findings provide a continuous spatiotemporal framework for mammalian fertilization, extended by initial observations in human oocytes.

Keywords:  ICSI; IVF; chromatin remodeling; cortical flow; cytoplasmic streaming; fertilization; live imaging; oocyte; sperm; zygote

DOI:  https://doi.org/10.1016/j.devcel.2026.06.015
Hum Reprod. 2026 Jul 15. pii: deag113. [Epub ahead of print]

Reply: Stem cell-based embryo models: scientific promise clashes with ethical reality.

Alfonso Martinez Arias, Nicolas Rivron, Shahragim Tajbakhsh, Josephine Johnston, Cantas Alev, Laure Bally-Cuif, Elvan Böke, Tommaso Cavazza, Emma Cave, David Cyranoski, Laurent David, Miguel A Esteban, Jianping Fu, Niels Geijsen, Nienke De Graeff, Jacob H Hanna, Nick Hopwood, Maneesha S Inamdar, Fredrik Lanner, Brigitte Leeners, Zhen Liu, Jean Leon Maitre, Gabriella Minchiotti, Naomi Moris, Megan Munsie, Kathy K Niakan, Olivier Pourquie, Vincent Pasque, Martin Pera, Yaojin Peng, Sophie Petropoulos, Sharad Ramanathan, Janet Rossant, Peter Rugg-Gunn, Mitinori Saitou, Karen Sermon, Jose Silva, Thorold Theunissen, Margherita Turco, John Wallingford, Hongmei Wang, Aryeh Warmflash, Jun Wu, Leqian Yu.

DOI: https://doi.org/10.1093/humrep/deag113
Adv Exp Med Biol. 2026 ;1517 151-164

Oocyte Kinetochores at the Nexus of Meiotic Drive and Segregation Fidelity.

Preethi Kunchala, Takashi Akera.

  Faithful chromosome segregation in oocytes relies on the precise coordination of core centromeric chromatin, dynamic kinetochore assembly, and spindle interactions. In meiosis I, sister kinetochores are mono-oriented toward the same spindle pole, allowing homologous chromosomes to bi-orient and segregate properly, whereas meiosis II exhibits conventional bi-orientation of sister chromatids. Stepwise assembly of kinetochore subcomplexes, Meikin-mediated mono-orientation, and protection of centromeric cohesion by Shugoshin ensure accurate segregation through meiotic divisions. These same structural and regulatory features, however, are also exploited by selfish centromeres to bias chromosome orientation on the oocyte spindle, leading to biased segregation to the egg and therefore to the next generation in violation of Mendel's Law of Segregation. We will review recent studies that have established a mechanistic framework for both accurate chromosome segregation and non-Mendelian segregation in oocytes, highlighting the central role of meiotic centromeres in female reproduction and evolutionary conflict.

Keywords:  Asymmetric Division; Centromere; Chromosome; Cohesin; Kinetochore; Meiosis; Non-Mendelian Transmission; Oocyte; Spindle Assembly Checkpoint

DOI:  https://doi.org/10.1007/978-981-92-1439-6_9
Adv Exp Med Biol. 2026 ;1517 59-81

Chromosome Architecture Defined by the Meiosis-Specific Cohesin in Mammalian Germ Cells.

Kei-Ichiro Ishiguro, Yasuhiro Fujiwara.

  Sister chromatid cohesion, established by the cohesin complex, is indispensable for accurate chromosome segregation in both mitosis and meiosis. Whereas mitosis relies predominantly on the canonical cohesin complex composed of SMC1α, SMC3, RAD21, and STAG1/2, meiosis employs specialized variants, including SMC1β, REC8, RAD21L, and STAG3. These meiosis-specific cohesins impart unique structural and regulatory properties essential for gametogenesis. They form the chromosome axis and organize chromatin loops, thereby providing the framework for homolog recognition, synapsis, and crossover control. At centromeres, meiotic cohesins secure proper kinetochore orientation and enable the stepwise release of cohesion across successive divisions. A striking feature of cohesins in oocytes is their extraordinary stability, persisting from fetal stages until adulthood, which underpins female reproductive longevity. Progressive loss of cohesin integrity with age contributes to aneuploidy, infertility, and congenital disorders, highlighting their clinical significance. This review synthesizes recent advances in defining the molecular composition, dynamics, and functions of meiotic cohesins in mammals. We emphasize their multifaceted roles in shaping chromosome architecture, examine mechanisms that link cohesin maintenance to reproductive aging, and outline key unresolved questions that may shed light on both the evolutionary innovations of meiosis and the origins of human reproductive disorders.

Keywords:  Aneuploidy; Chromosome Axis; Chromosome segregation; Cohesin; Hi-C; Meiosis; Sister chromatid cohesion; TAD; loop

DOI:  https://doi.org/10.1007/978-981-92-1439-6_5
PLoS Genet. 2026 Jul 14. 22(7): e1012237

High-resolution global recombination mapping in C. elegans reveals sexual dimorphisms shaped by meiotic chromosomal features and structures.

Zachary D Bush, John S Conery, Hannah R Wilson, Alice F S Naftaly, Devin Dinwiddie, Kenneth J Hillers, Diana E Libuda.

Crossover recombination events during meiosis repair DNA double-strand breaks and ensure accurate chromosome segregation in most organisms. For many species, the genomic distribution of crossovers is nonrandom and sexually dimorphic. While many species evolved kilobase-scale "hotspots" for crossover formation, the Caenorhabditis elegans genome lacks hotspots, and crossovers are enriched across megabase-scale domains. Further, genetic and cytological studies indicate the crossover frequency in C. elegans spermatogenesis is higher relative to oogenesis in many but not all genetic intervals. To determine the genomic features that contribute to the sexually dimorphic recombination landscape in the absence of hotspots, we defined and analyzed the recombination landscape across the whole genome in C. elegans using whole-genome sequencing and high-resolution recombination mapping in single worms bearing recombinant chromosomes from individual sperm and oocytes. We find that the spatial distribution of crossovers is sexually dimorphic on chromosomes I, II, and III, and that the global rate of double-crossover events is 4.7-fold higher in spermatocytes. Additionally, we find that pairing and synapsis may contribute to the sexually dimorphic crossover landscape. In comparison to the spermatocyte crossover landscape, a higher proportion of oocyte crossovers are formed in the domains directly adjacent to the pairing centers of each chromosome. Further, reducing the genetic dosage of the synaptonemal complex central region protein SYP-2, which is a meiotic chromosome structural protein required for homologous chromosome synapsis, reshapes the oocyte crossover landscape to resemble observations in wild-type spermatocytes. Finally, we found that spermatocyte crossovers are partially enriched in H3K36me3-marked euchromatic regions, while many oocyte crossovers are enriched in H3K27me3-marked heterochromatic regions. Taken together, our studies reveal how synaptonemal complex component dosage and local chromatin states influence crossover placement and the sex-specific regulation of meiotic recombination.

DOI: https://doi.org/10.1371/journal.pgen.1012237
bioRxiv. 2026 Jul 06. pii: 2026.07.03.736379. [Epub ahead of print]

Single-molecule m 6 A profiling reveals position-dependent mRNA regulation and non-canonical roles for Ythdf2 in early embryogenesis.

Sarah A Alshawi, Anna Delgado-Tejedor, Srihari Madhavan, Laia Llovera, Rebeca Medina, Cassandra Kontur, Eva Maria Novoa, Jean-Denis Beaudoin.

The maternal-to-zygotic transition (MZT) requires coordinated clearance and deadenylation of maternally deposited mRNAs, yet the underlying molecular mechanisms remain poorly understood. N6-methyladenosine (m 6 A) has emerged as a key regulator of maternal mRNA fate, but prior studies have relied on population-averaged short-read methods that cannot resolve modification state, poly(A) tail length, or isoform identity on the same molecule. Here, we employ nanopore direct RNA sequencing on zebrafish embryos across MZT to resolve the interplay between m 6 A deposition, mRNA clearance, and poly(A) tail length dynamics at single-molecule resolution. We find that 78% of expressed maternal genes harbor m 6 A-modified isoforms, significantly exceeding prior bulk estimates. Within-isoform comparisons demonstrate that m 6 A promotes mRNA decay, with CDS m 6 A contributing more to maternal mRNA clearance than 3'-UTR m 6 A. The positional context of m 6 A alone is sufficient to determine the temporal regulation of poly(A) tail lengths. CDS m 6 A constitutively suppresses tail length throughout MZT, while 3'-UTR m 6 A acquires shortening activity only after zygotic genome activation (ZGA). Transcriptomic analysis of ythdf2 knockout embryos reveals two unrecognized roles. Ythdf2 stabilizes m 6 A-marked maternal transcripts to set stoichiometry at MZT onset, and is also responsible for maintaining global poly(A) tail homeostasis prior to ZGA through an m 6 A-independent mechanism. Together, these findings define the single-molecule logic by which m 6 A modifications shape transcript fate during vertebrate MZT.

DOI: https://doi.org/10.64898/2026.07.03.736379
Adv Exp Med Biol. 2026 ;1517 167-176

Histone Modifications in Mammalian Early Embryos.

Takashi Ishiuchi.

  Early mammalian development entails one of the most extensive and physiologically relevant episodes of epigenomic reprogramming. Following fertilization, two highly specialized gametic epigenomes are reset to establish a totipotent zygotic state and are subsequently reorganized to enable lineage specification and pluripotency. A central component of this transition is the dynamic regulation of histone modifications that mark transcriptionally active and inactive chromatin. Studies in mouse embryos have revealed a distinctive sequence of events in which noncanonical, oocyte- and embryo-specific chromatin states are transiently established and then progressively replaced by canonical, somatic-like patterns around zygotic genome activation. However, comparative analyses across mammals demonstrate that several of these features, including broad noncanonical histone domains and Polycomb-mediated imprinting, are not universally conserved and differ substantially in humans and other species. In this chapter, we summarize recent findings on the dynamics of active and inactive histone marks during early embryogenesis, with a focus on principles derived from the mouse model and their limitations. We discuss how histone modifications contribute to transcriptional competence, repression, and lineage priming, how these processes vary across species, and how they together constitute an epigenomic "rebooting" that balances the erasure of parental memory with the preservation of essential regulatory information.

Keywords:  Chromatin dynamics; Cross-species comparison; Early embryogenesis; Epigenetic reprogramming; Histone modifications

DOI:  https://doi.org/10.1007/978-981-92-1439-6_10
Commun Biol. 2026 Jul 11.

Contribution of cohesins STAG1 and STAG2 to preimplantation development in mice.

Maria Solé-Ferran, Maria José Andreu, Daniel Giménez-Llorente, Jaime Muñoz, Sagrario Ortega, Ana Losada.

Cohesin complexes carrying either STAG1 or STAG2 display functional specificities in both cohesion and genome organization. While any variant is sufficient for cell viability, both are essential for murine embryonic development, and mutations in STAG1 and STAG2 are associated to human syndromes. The requirements and regulation of the cohesin variants in the first stages of development remain unknown. Here, we show that Stag1 and Stag2 gene products are stored in oocytes. Maternal STAG1 persists beyond the 2-cell stage while accumulation of STAG2 depends on zygotic transcription. Despite clear differences in STAG1:STAG2 ratio in the two lineages emerging from the first cell-fate decision, both maternal and zygotic STAG1 and STAG2 are dispensable for viability in preimplantation stages if the other variant is present. However, the absence of STAG2 increases DNA damage in zygotes and affects transcription in blastocysts. These early-stage alterations may contribute to defects leading to embryo lethality by mid-gestation.

DOI: https://doi.org/10.1038/s42003-026-10665-3
bioRxiv. 2026 Jul 09. pii: 2026.07.08.737289. [Epub ahead of print]

The microprotein Dafcin resembles influenza HA fusion peptide and regulates the size of storage lysosomes in the germline.

Kevin G Nyberg, Ryder Easterlin, Cooper W P Stringer, Hamdi K Küçükengin, Manny Joseph Widuch, Kyung Je Lee, Silpol Dhiantravan, Megan A Wong, Richard W Carthew.

Microproteins translated from short open reading frames are increasingly understood to play important roles in cell biology and development. Here, we describe a microprotein in Drosophila that is expressed in ovarian follicle cells which surround the developing oocyte. The Dafcin microprotein is predicted to form an amphipathic alpha-helix, a structure known to interact with lipid bilayers. Dafcin's structure most resembles the influenza HA fusion peptide, which induces negative curvature of endosomal membranes. Dafcin tagged with GFP localizes to the Golgi and is ultimately secreted from the follicle cells. Remarkably, this occurs without the microprotein having a secretory signal sequence. The protein is taken up into the oocyte by endocytosis, localizing to the inner face of storage lysosomes called yolk granules. Mutant analysis shows that Dafcin is required to limit the size of yolk granules. This may occur by inducing negative membrane curvature like HA peptide. In support, liposomes formed in vitro with both Dafcin and HA peptides are smaller in size.

DOI: https://doi.org/10.64898/2026.07.08.737289
J Vis Exp. 2026 Jun 26.

A workflow for Live Imaging and Quantitative Analysis of Acentrosomal Microtubule Networks in Drosophila Oocytes.

Jéssica Cabrita, Telmo Pereira, Ana Pimenta-Marques.

The microtubule (MT) cytoskeleton is essential for many cellular functions, including cell shape, polarity, migration, and division. While centrosomes function as the main MT-organizing center (MTOC) in dividing animal cells, many differentiated cells, including Drosophila oocytes, rely on acentrosomal pathways to assemble MT networks. In contrast to the extensive knowledge of MT organization in proliferating cells, little is known about how MT networks assemble without centrosomes. Drosophila oocytes provide a powerful model to study acentrosomal MT organization and dynamics. However, their dense MT network challenges conventional imaging. Live imaging enables real-time visualization of MT growth and orientation, yet standardized, analysis methods remain limited. Here, we present a live-imaging-based protocol to analyze MT growth dynamics in Drosophila oocytes using End-Binding Protein 1 (EB1)-Green Fluorescent Protein (GFP), a plus-end tracking protein that labels sites of active MT polymerization. High-resolution Airyscan confocal microscopy enables the detection of EB1 comets, while custom Fiji macros and Python scripts provide streamlined, reproducible quantification of comet density, velocity, length, and orientation. We validated this method by comparing control oocytes with those subjected to a cold-induced MT depolymerization, as well as Patronin mutants (CAMSAP in humans), a conserved MT minus-end stabilizer and a core component of non-centrosomal microtubule organizing centers (ncMTOC), as a positive control for impaired MT dynamics. Our analyses revealed region-specific MT dynamics, including anterior enrichment of EB1 comets and characteristic orientation biases, and confirmed the workflow's sensitivity to detecting subtle perturbations in MT growth. This approach provides a reliable, user-friendly framework for studying MT behavior in oocytes. The step-by-step protocol enables investigation of MT regulators in this context and may be adaptable to other differentiated cell types, such as neurons and epithelial cells, with appropriate optimization. More broadly, it supports mechanistic studies and genetic screens examining how diverse MT architectures underlie specialized cellular functions.

DOI: https://doi.org/10.3791/69983
Adv Exp Med Biol. 2026 ;1517 133-147

Asymmetric Chromosome Establishment and Segregation During Germline Stem Cell Division.

Yijun Liao, Xin Chen.

  In metazoans, gametogenesis produces the only cell type capable of transmitting both genetic and epigenetic information to offspring. This process represents one of the most extensive cellular differentiation programs, often originating from germline stem cells (GSCs), as in the female and male Drosophila and C. elegans gonads. These well-defined, unipotent germline lineages provide powerful in vivo models to study epigenetic regulation in multicellular organisms. During gametogenesis, epigenetic mechanisms balance cell differentiation and cellular plasticity. This review summarizes recent findings on how asymmetric sister chromatids are established and segregated during GSC division, the initial step of gametogenesis essential for reproduction in Drosophila and C. elegans. We focus on histones, a major carrier of epigenetic information, and discuss how their inheritance is regulated during GSC asymmetric divisions. Canonical histones and histone variants are dynamically incorporated into chromatin in a cell cycle- and genomic locus-specific manner, and these chromosome-bound epigenetic differences must coordinate with the mitotic machinery to ensure their proper partitioning. Finally, we speculate how these mechanisms may extend beyond the germline, assessing their conservation across species. Understanding these processes provides critical insights into how misregulation contributes to disease and how targeted manipulation could promote tissue homeostasis and regeneration.

Keywords:  Asymmetric cell division; C. elegans; Chromosome; DNA replication; Drosophila; Epigenetics; Germline stem cells; Histone; Histone variant

DOI:  https://doi.org/10.1007/978-981-92-1439-6_8
Am J Hum Genet. 2026 Jul 13. pii: S0002-9297(26)00241-7. [Epub ahead of print]

Landscape of parental postzygotic mutations across >11,000 rare disease trios.

O Isaac Garcia-Salinas, Katrina A Andrews, Rashesh Sanghvi, John A Sayer, Maria Torra I Benach, My H Pham, Aylwyn Scally, Hilary C Martin, Raheleh Rahbari.

  Early postzygotic mutations (PZMs) that arise after fertilization but prior to primordial germ cell specification may be present in both somatic and germ cells, causing mosaicism in a parent and constitutive inheritance in their offspring. In clinical family-trio whole-genome sequencing (WGS), such variants are systematically missed because their sub-heterozygous variant allele fraction (VAF) prevents heterozygous calling in the parent, while residual parental allele support disqualifies the variant as a candidate germline de novo mutation (DNM) in the child. Here, we developed a bioinformatic approach to ascertain parental PZMs from unfiltered DNM candidates in standard-depth (∼30×) trio WGS and applied it to 12,015 trios from the Genomics England 100,000 Genomes Project. We identified 1,015 high-confidence early autosomal parental PZMs, a large single-source catalog of this mutation class. These exhibited a monomodal VAF distribution centered around 5% in parental blood, consistent with empirically characterized ascertainment boundaries imposed by standard-depth sequencing and germline variant calling. PZMs showed no parental age or sex bias and displayed a mutational spectrum distinct from that of DNMs, with enrichment for C>A and T>A substitutions and depletion of T>C. Mutational signature analysis revealed that both mutation types are shaped by clock-like signatures SBS1 and SBS5 in similar proportions, suggesting that spectral differences reflect shifts within shared mutagenic processes. Exploratory genomic distribution analysis revealed a negative PZM association with GC content, in contrast to the positive association for DNMs. Among these, we found variants in DYNC1H1 and WT1 with potential clinical relevance that were missed by routine diagnostic pipelines.

Keywords:  early embryonic mutations; germline mutation; postzygotic mosaicism; rare disease genetics; trio sequencing; whole-genome sequencing

DOI:  https://doi.org/10.1016/j.ajhg.2026.06.015
Sci Adv. 2026 Jul 17. 12(29): eady2267

Satellite DNA sequence dictates pericentromere heterochromatin formation and function.

Piero Lamelza, Malena Parrado, Kathleen Leara, Ahmed Z Balboula, Thomas M Keane, Michael A Lampson.

Pericentromeres are heterochromatic regions adjacent to centromeres that ensure accurate chromosome segregation. Despite their conserved function, they are composed of rapidly evolving A/T-rich satellite DNA. To test the functional consequences of this rapid sequence evolution, we establish hybrid mouse embryos as a model system to compare divergent satellite arrays from distinct species in a common cytoplasm. We show that variation in satellite sequence impacts heterochromatin formation, recruitment of the Chromosome Passenger Complex (CPC), and interactions with the mitotic spindle. Differences in satellite DNA sequence alter pericentromere packaging by Polycomb Repressive Complex 1 (PRC1), as satellite arrays that recruit PRC1 are enriched for specific A/T sequences that the PRC1 AT-hook preferentially binds. Furthermore, PRC1 heterochromatin modifies pericentromere function by inhibiting recruitment of the CPC, increasing microtubule forces on kinetochores during mitosis. Our results provide a direct link between satellite DNA composition and mitotic chromosome behavior and highlight early embryogenesis as a critical point in development that is sensitive to satellite DNA evolution.

DOI: https://doi.org/10.1126/sciadv.ady2267
Adv Exp Med Biol. 2026 ;1517 17-25

Recent Progress in Characterizing Germline Mutations and Their Transmission Across Generations.

Ami Katanaya, Tomoatsu Takano, Mihoko Hosokawa, Li Jinghang, Shinichiro Chuma.

  Genome mutations in germ cells are fundamental to evolution and genetic diversity, while they also cause developmental abnormalities and genetic diseases, making their study essential in both biology and medicine. Research on germline mutations has advanced from classical genetic approaches, through transgenic model analyses, to next-generation sequencing, contributing to our understanding of germline mutations and their origins and inheritance. In particular, recent advances in sequencing technologies, including duplex sequencing and long-read sequencing, enable highly accurate detection of rare mutations and complex genomic alterations, including structural variants and repeat-associated changes, providing a more comprehensive view of mutational landscapes. Research progress has also been made in transposon regulation and spermatogonial stem cell dynamics, revealing additional layers of genome regulation in the germ line. These advances have greatly expanded our understanding of the germline genome and provide a foundation for future research in genetics, evolution, and reproductive biology.

Keywords:  Genome; Germline; Mutation; Reproduction; Stem

DOI:  https://doi.org/10.1007/978-981-92-1439-6_2
Hum Reprod. 2026 Jul 15. pii: deag114. [Epub ahead of print]

Metabolic imaging for gamete and embryo assessment through advanced microscopy technologies: a novel avenue for artificial intelligence?

Fabrizzio Horta, Denny Sakkas, Shannon Handley, Yaoxi Xiong, Bettina Mihalas, Rebecca Deans, Roger J Hart, Robert B Gilchrist, Ewa M Goldys.

  Infertility affects approximately one in six people globally and demand for ARTs, is expected to rise as parenthood is increasingly delayed. However, ART success remains constrained by gamete and embryo quality, female age, and biological factors beyond chromosomal status alone, highlighting the need for non-invasive methods that can complement current morphology-based and genetic approaches. Because gamete and embryo developmental competence is tightly coupled to cellular metabolism, label-free metabolic imaging has emerged as a promising strategy to assess developmental potential through endogenous autofluorescence of reduced nicotinamide adenine dinucleotide/phosphate [NAD(P)H] and oxidized flavins (FAD), which provide optical proxies of redox balance, mitochondrial activity, and oxidative metabolism. This invited mini-review synthesizes the biochemical basis of NAD(P)H/FAD autofluorescence signals, relates these readouts to the unique metabolic programs of oocytes, embryos across preimplantation development, and sperm, and reviews reproductive studies using fluorescence lifetime imaging microscopy, hyperspectral microscopy, and emerging light-sheet fluorescence microscopy. We discuss practical and interpretive challenges, including modality-dependent signal biases and recent consensus efforts towards standardization. Evidence linking metabolic signatures to reproductive ageing, developmental potential, and embryo ploidy status suggests that metabolic imaging, particularly when paired with artificial intelligence (AI), could enable automated, objective decision support for gamete and embryo selection. Finally, we briefly outline how AI could convert complex metabolic imaging data into clinically interpretable decision-support outputs for embryo ranking and risk stratification. Advances in rapid volumetric imaging, microsystems, and AI may support future ART workflows aimed at improving efficiency, accessibility, and cost-effectiveness.

Keywords:  ART; embryos; metabolic imaging; metabolism; microsystems; oocyte; sperm

DOI:  https://doi.org/10.1093/humrep/deag114
Adv Exp Med Biol. 2026 ;1517 195-208

Nucleoskeletal Proteins in Early Embryogenesis.

Yasuki Miyagawa, Kei Miyamoto.

  Embryogenesis begins with fertilization, resulting in a totipotent zygote that undergoes a complex series of cellular and molecular events toward the development of a complete organism. During this period, critical events such as zygotic genome activation and cell fate specification occur, characterized by dynamic changes in gene expression programs. Regulation of gene expression is generally explained by chromatin-based mechanisms orchestrated in nuclei. To note, non-chromatin nuclear proteins, referred to as nucleoskeletal proteins, emerge as key players for shaping nuclear and chromatin structures. The nucleoskeleton consists of multiple proteins, and its dynamics are important for establishing cell-type-specific nuclear structure, genome organization, and gene expression patterns. Recent studies have highlighted that nucleoskeletal proteins, particularly lamins and nuclear actin, play diverse and critical roles during early embryogenesis. Furthermore, a growing body of evidence suggests that nuclear architecture itself can actively influence gene expression and embryonic development. In this review, we focus on the nuclear structure of early vertebrate embryos from the viewpoint of the nucleoskeleton. We summarize current findings regarding the dynamics and functions of nucleoskeletal proteins during embryogenesis and further discuss how these constitutional components can affect gene expression and developmental programs.

Keywords:  Early embryogenesis; Lamin; Nuclear actin; Nuclear structure; Nucleoskeleton

DOI:  https://doi.org/10.1007/978-981-92-1439-6_12
Sci Adv. 2026 Jul 17. 12(29): eaee0143

Spaceflight multi-omics reveals vulnerabilities of human germ cell development.

Ying Li, Hui Gao, Jie Xiong, Nan Wang, Yongchun Yuan, Linjun Wang, Jinzhong Xu, Wenze Huang, Gikin Tan, Xiaojuan He, Qiangfeng Cliff Zhang, Tao Zhang, Kehkooi Kee.

Understanding the impact of spaceflight on human reproduction is critical for interplanetary exploration, yet technical barriers have limited direct studies of germ cell biology in orbit. Here, we utilized an automated bioreactor that supported long-term differentiation of human embryonic stem cells into human induced primordial germ cells (hiPGCs), human induced ovarian follicles (hiOFs), and human induced spermatogonial stem cells (hiSSCs) aboard spacecraft. Integrated real-time imaging, programmable medium perfusion, and in situ preservation enabled time-resolved multi-omics analysis. During missions on China's Tianzhou-1 and Tianzhou-6 spacecraft, spaceflight reduced hiPGC specification efficiency by approximately 50% and suppressed hiSSC proliferation by 26%. Transcriptome-translatome coordination revealed cell-type-specific dysregulation of extracellular matrix organization, microtubule dynamics, and lipid metabolism. Whole-exome sequencing and DNA methylome analysis demonstrated preserved genomic integrity despite these functional perturbations. These findings provide direct evidence that spaceflight perturbs human germ cell development and establish a scalable framework for monitoring cellular adaptation during deep-space missions.

DOI: https://doi.org/10.1126/sciadv.aee0143
Vet Res Commun. 2026 Jul 13. pii: 455. [Epub ahead of print]50(5):

Advances in bovine oocyte in vitro maturation: mechanisms and strategies.

Mostafa Pournourali, Abolfazl Shirazi, Nahid Mizban, Sara Borjian-Boroujeni, Ali Sarvari, Hamideh Adeldust, Mohammadmehdi Barfar, Gaia Cecilia Luvoni.

  In vitro maturation (IVM) of bovine oocytes remains a major limiting step in in vitro embryo production (IVP), largely because current culture systems fail to fully reproduce the dynamic biochemical and biophysical conditions of the follicular environment. Successful maturation requires precise coordination of nuclear and cytoplasmic events, supported by active communication between the oocyte and surrounding cumulus and granulosa cells. Intrinsic factors, including follicle size, metabolic status, mitochondrial function, and one-carbon metabolism (OCM), together with extrinsic elements such as hormonal cues, oxidative balance, and culture conditions, collectively determine oocyte competence. Among these, OCM plays a central role by regulating methyl donor availability, redox homeostasis, nucleotide synthesis, and epigenetic programming, thereby influencing early embryonic development. Recent advances aim to bridge the gap between in vivo and in vitro maturation. Strategies such as antioxidant supplementation, growth factor enrichment, and simulated physiological oocyte maturation (SPOM) have been reported to improve synchrony between nuclear and cytoplasmic maturation, although their effects remain variable across studies. Emerging technologies-including extracellular vesicle (EV) supplementation and microfluidic culture platforms-offer biomimetic environments that may enhance metabolic stability, restore physiological signaling, and improve embryo developmental potential. This review synthesizes current knowledge on the molecular and cellular mechanisms governing bovine oocyte maturation, critically evaluates intrinsic and extrinsic factors affecting IVM outcomes, and highlights innovative approaches that may increase oocyte competence and IVP efficiency. Overall, integrating omics-guided optimization, microfluidic systems, EV-based communication, and strengthened OCM pathways represents a promising yet still evolving direction for improving embryo yield and advancing sustainable cattle production.

Keywords:  Bovine oocyte maturation; Cumulus–oocyte complex; Embryo developmental competence; In vitro maturation (IVM); Oocyte competence

DOI:  https://doi.org/10.1007/s11259-026-11399-7