bims-cebooc 2026-09-13 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–09–13
eight papers selected by
Gabriele Zaffagnini, Universität zu Köln

Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats.
Spatially ordered zygotic genome activation fulfills embryo quality control.
Dynamic Remodeling of Oocyte-Granulosa Cell Communication During Bovine Folliculogenesis Revealed by Transcriptomic Meta-Analyses.
Epigenetic Reprogramming and Zygotic Genome Activation in Human Preimplantation Development: Mechanisms, Models, and Translational Prospects.
The Small but Versatile Cyclin-Dependent Kinase Subunit CKS: C. elegans CKS-1 Regulates Anaphase Onset and Is Required for Anaphase B During Oocyte Meiosis.
Handle with care: packaging the oocyte epigenome for the next generation.
Postnatal Ketone Deficiency Impairs Adult Oocyte Quality via Enhancing Histone Acetylation in Malnourished Mice.
Nodal/Smad2 signaling maintains diapause in the mouse embryo.

Aging Cell. 2026 Sep;25(9): e70710

Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats.

Subhasri Biswas, Hoang V M Nguyen, Aubrey Converse, Satoshi Matsuzaki, Michael T Kinter, Kenneth M Humphries, Willard M Freeman, Sarah R Ocañas, Arlan Richardson, Francesca E Duncan, Tommy L Lewis, Michael B Stout.

  Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose women to age-associated comorbidities. Despite these observations, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it remains unknown if naturally occurring mitochondrial genetic variation influences the trajectory of ovarian aging. To address this, we compared two genetically heterogeneous rat cohorts (OKC-HETB and OKC-HETW) that differ in mitochondrial haplotype on a randomized but equivalently distributed nuclear background. The OKC-HETW haplotype was associated with accelerated loss of primordial follicles and pathological remodeling marked by fibrosis, macrophage infiltration, and multinucleated giant cells. These tissue-level pathologies were paralleled by mitochondrial dysfunction, characterized by decreased respiratory complex activity, ATP production, and mtDNA copy number. Mechanistically, we identified a haplotype-specific defect in mitochondrial genome maintenance. Although TFAM expression was normal, and total TFAM protein was elevated, OKC-HETW ovaries showed reduced mitochondrial TFAM abundance, TFAM-mtDNA binding, and TOMM20, suggesting that impaired TOMM20-mediated import is associated with compromised mitochondrial genomic stability. Longitudinal transcriptomic and proteomic analyses further indicate that mitochondrial haplotype influences the rate of ovarian aging, with OKC-HETW ovaries showing accelerated activation of inflammatory and fibrotic pathways alongside suppressed proteostasis and mitochondrial function. These defects corresponded to impairments in ovulation and a trend toward worsening oocyte quality. Collectively, our findings identify mitochondrial haplotype as a heritable modifier of ovarian aging rate that acts in concert with the nuclear genome, and a putative target for preserving ovarian function and female healthspan.

Keywords:  anti‐Müllerian hormone; follicle; haplogroup; menopause; oxidative phosphorylation; rat; reproductive senescence

DOI:  https://doi.org/10.1111/acel.70710
J Cell Biol. 2026 Oct 05. pii: e202412222. [Epub ahead of print]225(10):

Spatially ordered zygotic genome activation fulfills embryo quality control.

Wenchao Qian, Hui Chen, Hongju Lee, Matthew C Good.

Early embryo development features autonomous, maternally driven cell divisions that self-organize the multicellular blastula or blastocyst tissue. Maternal control cedes to the zygote starting with the onset of widespread zygotic genome activation (ZGA), which is essential for subsequent cell fate determination and morphogenesis. Intriguingly, although ZGA onset is highly regulated at the level of the whole embryo, it can be non-homogenous and precisely patterned at the single-cell level. We previously demonstrated a stereotyped spatial and temporal ordering of ZGA in a model vertebrate embryo. Unknown, however, was whether this precise ZGA patterning was required for development. To address this fundamental question, we devised a strategy to spatially control cell divisions that perturb blastula embryo organization. We demonstrate the feasibility of spatially inverting the cell size pattern of embryos and find that these inverted embryos exhibit a flipped pattern of ZGA. Mispatterned ZGA along the animal-vegetal axis triggers embryo apoptosis, revealing that gastrula embryos have a built-in quality control system to sense inappropriate ZGA patterning, including regionalized defects in transcriptional onset. The quality control response is nonautonomous, dependent on an anti-apoptotic signal that suppresses cell death outside the animal hemisphere. These results reveal the requirement of properly patterned ZGA for normal development and the existence of a surveillance system of embryo quality control exquisitely tuned to the spatial and temporal ordering of genome activation and zygotic gene expression.

DOI: https://doi.org/10.1083/jcb.202412222
FASEB J. 2026 Sep 30. 40(18): e72289

Dynamic Remodeling of Oocyte-Granulosa Cell Communication During Bovine Folliculogenesis Revealed by Transcriptomic Meta-Analyses.

Noemi Monferini, Ludovica Donadini, Pritha Dey, Federica Franciosi, Valentina Lodde, Maria Belen Rabaglino, Alberto Maria Luciano.

  Ovarian folliculogenesis relies on tightly coordinated communication between the oocyte and surrounding granulosa cells, yet how this molecular dialogue is remodeled during follicle development remains poorly understood. Here, we reconstructed stage-specific ligand-receptor communication networks through a transcriptomic meta-analysis integrating bovine secondary, early antral, and middle antral follicles. Our analyses revealed that oocyte-granulosa cell communication undergoes progressive remodeling during folliculogenesis, with distinct signaling programs characterizing successive developmental stages. Secondary follicles were predominantly associated with extracellular matrix organization, cell adhesion, and early metabolic regulation. During the early antral stage, signaling shifted toward lipid, steroid, and vitamin metabolism, identifying this phase as a major metabolic transition. Middle antral follicles exhibited a marked increase in communication complexity, with enrichment of PI3K-AKT, mTOR, RAS, Hippo, and cell adhesion pathways accompanying the acquisition of developmental competence. Additional analyses of Brilliant Cresyl Blue-classified cumulus-oocyte complexes identified competence-associated ligand-receptor interactions, while independent validation using the EmbryoGENE dataset confirmed stage-specific expression patterns and highlighted CD47, FGF21, and GPC6 as candidate regulators of oocyte developmental competence. This study provides a comprehensive transcriptomic framework describing the dynamic remodeling of oocyte-granulosa cell communication during bovine folliculogenesis. Beyond confirming established signaling pathways, it identifies novel candidate interactions and offers a biologically grounded resource to guide future functional studies and the optimization of in vitro follicle and cumulus-oocyte complex culture systems.

Keywords:  cell–cell signaling ligand–receptor interactions; cumulus cell; developmental competence; folliculogenesis; oocyte–granulosa cell communication; ovary

DOI:  https://doi.org/10.1096/fj.202603316RR
Reprod Med Biol. 2026 Jan-Dec;25(1):25(1): e70095

Epigenetic Reprogramming and Zygotic Genome Activation in Human Preimplantation Development: Mechanisms, Models, and Translational Prospects.

Atsushi Fukuda.

Purpose: Early human embryogenesis unfolds through a tightly coupled sequence of events-clearance of maternal transcripts, remodeling of parental chromatin, zygotic genome activation (ZGA), lineage segregation, implantation, and post-implantation patterning-accompanied by epigenetic reprogramming, including X-chromosome dosage compensation around the time of implantation. This review aims to synthesize recent advances in understanding this developmental program and to consider their implications for reproductive medicine.
Methods: I review recent literature on human early embryogenesis, with particular emphasis on findings enabled by single-cell genomics and stem-cell-based embryo modeling, and integrate these insights to identify human-specific features of early development.
Results: These approaches have made previously inaccessible aspects of human early embryogenesis experimentally tractable, revealing molecular and epigenetic features that distinguish human development from that of model organisms, including species-specific dynamics of ZGA, maternal transcript clearance, chromatin reprogramming, and X-chromosome dosage compensation.
Conclusions: Advances in single-cell genomics and embryo modeling are transforming our understanding of human early embryogenesis. Building on these insights, while recognizing their current limitations, I propose a vision for improving reproductive medicine, including the potential for next-generation embryo selection strategies.

DOI: https://doi.org/10.1002/rmb2.70095
Bioessays. 2026 Sep;48(9): e70180

The Small but Versatile Cyclin-Dependent Kinase Subunit CKS: C. elegans CKS-1 Regulates Anaphase Onset and Is Required for Anaphase B During Oocyte Meiosis.

Jie Yang, Bruce Bowerman.

  The cyclin-dependent kinase subunit (CKS) remains the least well-understood component of the tripartite cyclin-dependent kinase (CDK) complexes that specify the proper sequence of events required to duplicate and segregate genomes during eukaryotic cell division. Our recent investigation of CKS requirements during Caenorhabditis elegans oocyte meiosis I and II documents an essential role for CKS in the execution of anaphase B and expands the known range of CKS influence on cell cycle regulation to a third class of E3 ligases. Our findings also further document how C. elegans oocytes use very different mechanisms to progress through these two sequential cell divisions that ultimately produce a haploid oocyte. In this Think Again article, we discuss our findings as they relate to previous studies of CKS in different model systems.

Keywords:  anaphase; caenorhabditis elegans; cell biology; cell cycle; kinase; oocyte

DOI:  https://doi.org/10.1002/bies.70180
Reprod Fertil Dev. 2026 Sep 29. pii: RD26098. [Epub ahead of print]38(14):

Handle with care: packaging the oocyte epigenome for the next generation.

Chloe A Edwards-Lee, Ellen G Jarred, Patrick S Western.

  During oocyte growth, substantial epigenetic programming occurs to establish a distinctive epigenome including appropriately patterned DNA methylation and histone modifications. Oocyte epigenetic programming must be tightly spatiotemporally regulated to ensure that a wide variety of epigenetic modifiers correctly establish their respective modifications to mediate precise control of gene expression. Furthermore, epigenetic modifications in oocytes include canonical and non-canonical genomic imprints, which are transmitted through meiosis to offspring. Significantly, disruptions in oocyte epigenetic programming can cause aberrant developmental outcomes in the next generation mediated by altered imprinting. Polycomb repressive complex 2 is an important epigenetic modifier that establishes histone 3 lysine 27 trimethylation and non-canonical imprints during mouse oogenesis, which are important for normal offspring development. While it is widely recognised that altered oocyte epigenetic programming can disrupt offspring development, mechanisms controlling maternal epigenetic inheritance remain poorly understood. The possibility remains that non-canonical imprinting exists in humans, although this requires confirmation. This review discusses mouse and human oocyte epigenetic programming including interactions between various epigenetic modifiers and modifications that form the unique oocyte epigenome. Understanding how oocyte epigenetic programming is regulated will be crucial in discerning how changes to the oocyte epigenome can disrupt epigenetic memory and alter developmental outcomes in offspring.

Keywords:  H3K27me3; embryonic ectoderm development; epigenetics; maternal epigenetic inheritance; offspring development; oocyte epigenetic programming; oogenesis; polycomb; polycomb repressive complex 2

DOI:  https://doi.org/10.1071/RD26098
J Biol Chem. 2026 Sep 08. pii: S0021-9258(26)02407-5. [Epub ahead of print] 113535

Postnatal Ketone Deficiency Impairs Adult Oocyte Quality via Enhancing Histone Acetylation in Malnourished Mice.

Xin-Ge Zhang, Ming-Zhi Li, Han Sha, Shi-Yao Tao, Yuan Qiao, Qi-Wen Yang, Li-Rong Wang, Xiao-Qian Zhang, Dan-Yang Chong, Zhi-Bin Hu, Yuan Lin, Xiu-Feng Ling, Chao-Jun Li.

Early postnatal life is important for reproductive development, but the effects of early-life nutrition on female reproductive capacity remain largely unknown. Here, we investigated whether neonatal ketone body deficiency affects adult oocyte quality using a lactational malnutrition model and Hmgcs2-deficient mice. We found that impaired neonatal ketogenesis caused long-lasting impairments in female reproductive function, including reduced ovarian reserve, decreased oocyte developmental competence, altered hormone levels, and impaired embryo development. Neonatal β-hydroxybutyrate (β-HB) supplementation partially improved these reproductive abnormalities, indicating an important role of ketone metabolism during early ovarian development. Transcriptomic and epigenomic analyses showed that Hmgcs2 deficiency disrupted histone H3 acetylation homeostasis in oocytes. These Ace-H3 changes were enriched in genes related to oxidative stress and apoptosis and were accompanied by transcriptional alterations. β-HB supplementation partially restored the altered Ace-H3 patterns. Together, our findings reveal that ketone bodies regulate oocyte development by connecting early-life nutrition with epigenetic regulation.

DOI: https://doi.org/10.1016/j.jbc.2026.113535
Dev Cell. 2026 Sep 09. pii: S1534-5807(26)00322-9. [Epub ahead of print]61(9): 1762-1763

Nodal/Smad2 signaling maintains diapause in the mouse embryo.

Bruce D Murphy.

Embryonic diapause is a reversible dormant state that allows mammalian blastocysts to survive periods of environmental or metabolic stress. In this issue of Developmental Cell, Furlan et al.1 report that Nodal/Smad2 signaling sustains diapause by repressing Pparg-driven lipid storage in the blastocyst.

DOI: https://doi.org/10.1016/j.devcel.2026.08.011