bims-cebooc 2026-01-04 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–01–04
seven papers selected by
Gabriele Zaffagnini, Universität zu Köln

Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging.
Organization of replicated chromosomes by DNA loops and sister chromatid cohesion.
Microscale pressure measurements and optical coherence tomography reveal time-dependent biomechanical stages of ovulation in mice.
Influencing Ovarian Aging in Reproductive Medicine: Promise, Evidence, and Unresolved Questions.
Bridges under construction: the dynamics of ring canal expansion during Drosophila oogenesis.
A computational framework to study EGFR signaling distribution in egg chambers during dynamic interactions between soma and germline.
Ovotoxicant VCD disrupts oocyte meiosis in mice by impairing m6A/IGF2BP3-mediated mRNA stability.

Aging Cell. 2026 Jan;25(1): e70333

Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging.

Shweta S Dipali, Aubrey Converse, Madison Q Gowett, Pratik Kamat, Emily J Zaniker, Abigail Fennell, Teresa Chou, Michele T Pritchard, Mary Zelinski, Jude M Phillip, Francesca E Duncan.

  Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered an ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Self-organized ovarian somatic organoids maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly, matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregulation of cell adhesion pathways, indicative of increased cellular stiffness that may impair organoid aggregation. Cellular morphology, which is regulated by the cytoskeleton, significantly changed with age and in response to actin modulation. Moreover, actin modulation altered organoid aggregation efficiency. Overall, ovarian somatic organoids have advanced knowledge of cellular contributions to ovarian aging.

Keywords:  actin; cellular stiffness; organoid; ovary; reproductive aging; stroma

DOI:  https://doi.org/10.1111/acel.70333
Nat Rev Mol Cell Biol. 2026 Jan 02.

Organization of replicated chromosomes by DNA loops and sister chromatid cohesion.

Fena Ochs, Daniel W Gerlich.

Cohesin is a key regulator of three-dimensional genome organization, contributing to gene regulation, recombination, DNA repair and chromosome segregation. Like other members of the evolutionary conserved structural maintenance of chromosomes (SMC) protein-complex family, cohesin folds DNA through motor-driven loop extrusion. Cohesin has a unique, second activity of genome organization: it physically links sister chromatids together in replicated chromosomes, a process termed sister chromatid cohesion. Sister chromatid cohesion and loop extrusion are mediated by two distinct pools of cohesin, which share common core subunits, but associate with distinct regulatory subunits to interact with chromosomes in fundamentally different ways. In this Review, we discuss how sister chromatid cohesion is established and regulated, and how an interplay between cohesion and chromatin loops organizes replicated chromosomes. We also discuss how cohesion supports chromosome segregation in mitosis and meiosis, and how it contributes to DNA double-strand break repair and age-related oocyte aneuploidy. We outline recent technological advances that provide new opportunities to study cohesion and the conformation of replicated chromosomes, and we provide a perspective on how these tools might be applied to answer fundamental questions in cohesin biology.

DOI: https://doi.org/10.1038/s41580-025-00933-1
iScience. 2025 Dec 19. 28(12): 114086

Microscale pressure measurements and optical coherence tomography reveal time-dependent biomechanical stages of ovulation in mice.

Emily J Zaniker-Gomez, Zihang Yan, Jing Yang, Darryl L Russell, Hao Zhang, Sean X Sun, Francesca E Duncan.

  During ovulation, antral follicles undergo coordinated remodeling that results in egg release and corpora lutea formation, which are key processes for fertility and endocrine function. Using an ex vivo murine ovulation model integrated with time-lapse imaging, microscale pressure sensing, and optical coherence tomography (OCT), we characterized and quantified the sequence of mechanical events driving follicle rupture. We demonstrated that ovulation begins with a hyaluronan-dependent rise in intrafollicular pressure, followed by antral expansion and thinning of the follicle wall, which leads to elevated wall stress preceding rupture. Additionally, we characterized changes in ovulatory biomechanical dynamics associated with advanced reproductive age. By mapping the physical timeline of ovulation, this work establishes a framework for understanding the biomechanical regulation of egg release and provides insight into how age-related changes in follicular biomechanics may contribute to infertility.

Keywords:  biological sciences; chemistry; health profession; medicine; pharmaceutical science; physics; veterinary medicine

DOI:  https://doi.org/10.1016/j.isci.2025.114086
Fertil Steril. 2025 Dec 29. pii: S0015-0282(25)02309-X. [Epub ahead of print]

Influencing Ovarian Aging in Reproductive Medicine: Promise, Evidence, and Unresolved Questions.

Allison A Eubanks, Eric Widra, Kara N Goldman, Elnur Babayev, Francesca E Duncan.

  Ovarian aging is a fundamental biological constraint on female fertility, driven by depletion of the primordial follicle pool and progressive alterations in the ovarian microenvironment. In recent years, a range of intraovarian interventions aimed at modifying ovarian aging- including platelet-rich plasma, autologous stem cell-based approaches, and mitochondrial transfer- have gained clinical and commercial attention. These strategies are supported by biologic hypotheses and early changes in surrogate markers such as anti-mullerian hormone (AMH) and antral follicle count, yet their clinical significance remains uncertain. This Views and Reviews critically evaluates the evidence supporting these interventions, emphasizing the distinction between transient follicular activation and true modification of reproductive aging. Clinical data are integrated with emerging mechanistic insights from aging biology, including nutrient-sensing pathways, partial epigenetic reprogramming, and ovarian fibrosis as a modifiable determinant of ovarian function. Across modalities, improvements in surrogate outcomes have not reliably translated into gains in embryo competence, euploidy, or live birth, and safety data remain limited, with procedural and infectious risks that warrant careful consideration. We conclude that routine clinical use of intraovarian aging-targeted interventions is premature. Future progress will require standardized protocols, adequately powered randomized trials with live birth endpoints, and rigorous assessment of both efficacy and risk.

Keywords:  Assisted reproduction; Ovarian aging; Ovarian microenvironment; Platelet-rich plasma; Reproductive longevity

DOI:  https://doi.org/10.1016/j.fertnstert.2025.12.020
Dev Biol. 2025 Dec 31. pii: S0012-1606(25)00352-5. [Epub ahead of print]

Bridges under construction: the dynamics of ring canal expansion during Drosophila oogenesis.

Kari Price, Lindsay Lewellyn.

Intercellular bridges connect cells within tissues and organs across the animal kingdom, where they play important roles in cell-cell communication and coordination. Some of the most well-studied intercellular bridges are the ring canals that connect germline cells within the developing Drosophila egg chamber. The genetic, imaging, and biochemical tools available within this model system have generated a wealth of information about the proteins, pathways, and structures that regulate ring canal formation, stability, and expansion. In this review, we describe the important contributions that have been made to our understanding of ring canal biology, with an emphasis on the mechanisms that promote ring canal expansion. We describe accessible and reliable tools available to study these structures as well as ways in which more modern genetic, imaging, biochemical, and bioinformatics-based approaches could be applied to the study of ring canals within the egg chamber or in other tissues or organisms.

DOI: https://doi.org/10.1016/j.ydbio.2025.12.021
PLoS Comput Biol. 2025 Dec 29. 21(12): e1013802

A computational framework to study EGFR signaling distribution in egg chambers during dynamic interactions between soma and germline.

Nastassia Pouradier Duteil, Nicole T Revaitis, Mathew G Niepielko, Eric A Klein, Nir Yakoby, Benedetto Piccoli.

Forming organs requires the appropriate distribution of spatiotemporal signals leading to tissue patterning and morphogenesis. Advances in genetic tools contributed to our understanding of cell signaling and their associated genes. Yet, due to technical challenges, the contribution of dynamic morphological transformations of tissues during organ formation remains widely unexplored. Here, we develop a new mathematical approach to understand the variables that shape the dynamic distribution of ligand and signaling. We use the TGF-α-like ligand Gurken (GRK) and the activation of the epidermal growth factor receptor (EGFR) during Drosophila oogenesis to build the model. Our model accounts for GRK secretion from a moving source, its diffusion in the perivitelline space, and the activation of EGFR in the overlaying follicle cells. Furthermore, we also capture the rapid growth of the oocyte, which was a major challenge to integrate into a model. We modeled the dynamic distribution of GRK and EGFR activation by a series of mathematical equations. We used this model to study how perturbations of the egg chamber's morphological evolution impact cell signaling, which could not be achieved via genetic perturbation. We found that the relative movement of the follicle cells and the oocyte contributes to the distribution of EGFR signaling activation.

DOI: https://doi.org/10.1371/journal.pcbi.1013802
Commun Biol. 2025 Dec 27.

Ovotoxicant VCD disrupts oocyte meiosis in mice by impairing m6A/IGF2BP3-mediated mRNA stability.

Yang Li, Yuling Zhou, Jian Liu, Guangning Nie, Fangping Cheng, Hongyan Yang.

Environmental toxicants pose a significant threat to female reproductive health, yet the molecular mechanisms through which they impair oocyte quality are often unclear. Although the industrial chemical 4-vinylcyclohexene diepoxide (VCD) is known to cause ovarian follicle loss, how it disrupts essential processes such as meiosis remains poorly understood. Here, we show that VCD exposure triggers meiotic failure in mouse oocytes by altering a key RNA modification pathway known as m6A methylation. VCD treatment reduces ovarian reserve, elevates oxidative stress, and causes severe chromosome segregation defects. We find that VCD dysregulates the expression of m6A writers and erasers, leading to altered methylation of transcripts critical for cell division and meiosis. Specifically, VCD downregulates the RNA-binding protein IGF2BP3, which destabilizes target genes required for chromosome alignment and spindle assembly. Our results reveal how an environmental toxin can cause epitranscriptomic dysregulation and meiotic failure, providing a new perspective on pollutant-induced fertility decline. This work highlights the m6A pathway as a potential therapeutic target and underscores the broader reproductive risks posed by chemical exposures.

DOI: https://doi.org/10.1038/s42003-025-09187-1