bims-cebooc 2025-08-24 papers

Issue of 2025–08–24
five papers selected by
Gabriele Zaffagnini, Universität zu Köln

Biophys J. 2025 Aug 18. pii: S0006-3495(25)00524-7. [Epub ahead of print]

Direct mechanical communication of cellular to nuclear shape in oocytes.

Bart E Vos, Yamini Vadapalli, Till Muenker, Ida Marie Astad Jentoft, Elena Todisco, Mohammad Amin Eskandari, Melina Schuh, Peter Lenart, Timo Betz.

The mechanical properties of the cytoplasm and nucleoplasm are crucial for the correct and robust functioning of a cell and play a key role in understanding how mechanical signals are transferred to the nucleus. Here, we demonstrate remarkable shape mimicry between the cellular and nuclear shape of oocytes, following the externally applied deformation without direct contact between the cell cortex and the nucleus. This effect arises from a surprisingly soft and fluid-like nucleoplasm that barely resists external strain, while the viscoelastic cytoplasm drives shape transmission. Comparative studies in jellyfish, starfish, and mouse oocytes reveal that lower cytoplasmic elasticity in jellyfish leads to reduced nuclear shape mimicry, highlighting the role of cytoplasmic mechanics in nuclear deformation.

DOI: https://doi.org/10.1016/j.bpj.2025.08.012

Commun Biol. 2025 Aug 19. 8(1): 1245

Single cell multiomics approach to analyze replication timing and gene expression in mouse preimplantation embryos.

Anala V Shetty, Clifford J Steer, Walter C Low.

Analysis of a cell's replication timing (RT) provides insight into how genes replicate, early or late, during the S-phase of the cell cycle. RT is cell-type specific, inheritable, and has been correlated to gene expression in normal and diseased states. However, most studies have been limited to somatic cells. Very little is known about RT control in early mouse embryos, and how it correlates with the start of transcription during zygote gene activation (ZGA), at the 2-cell stage. In this study, we develop an in-house single-cell multiomics approach to simultaneously analyze RT and gene expression in individual cells of the mouse 1-cell, 2-cell, and 4-cell embryos. We detect that RT is established at the 1-cell stage prior to ZGA. Surprisingly, we observe that the coordinated RT and gene expression control is different in early totipotent embryos, compared to previously published studies in somatic cells. Late replicating regions correlate with higher gene expression and open chromatin in the early developing embryos. Lastly, we perform an integrated pseudo time trajectory analysis combining RT and gene expression information per cell.

DOI: https://doi.org/10.1038/s42003-025-08694-5

J Biol Chem. 2025 Aug 14. pii: S0021-9258(25)02449-4. [Epub ahead of print] 110598

Chromatin deactivation in pre-granulosa cells contributes to primordial follicle formation.

Xuzhao Wang, Xin Qiu, Yuxiao Ma, Xiaotong Guo, Jiahui Wei, Feiyi Wang, Heng Wang, Guiyu Zhu.

The establishment and maintenance of the primordial follicle pool are critical for determining the ovarian reserve in females, ensuring efficient oocyte production particularly in farm animals such as egg-laying chickens. This process involves the breakdown of germ cell cysts and the encapsulation of individual oocytes by somatic pre-granulosa cells to form primordial follicles, which then enter a lasting state of dormancy. The proper development of pre-granulosa cells is essential for their interaction with and protection of oocytes, facilitating successful follicle formation. How pre-granulosa cells reorganize to contribute to primordial follicle formation and their quiescence establishment remain poorly understood. This study investigated gene expression and chromatin regulation in chicken pre-granulosa cells during the primordial follicle establishment to identify epigenetic mechanisms that could enhance ovarian reserve and improve egg production. ChIP-seq assay revealed a global reduction in active chromatin as evidenced by the depletion of H3K27ac deposition. This chromatin de-activation caused the down-regulation of target genes involved in promoting cell apoptosis and blocking cell adhesion, thereby supporting cell survival and enhancing cell-cell communications necessary for follicle assembly. Further validation using an ex vivo chicken ovary organ culture system demonstrated that prolonged chromatin activation, achieved through histone deacetylase inhibitor-mediated chromatin acetylation, significantly reduced the number of primordial follicles and resulted in the persistence of unruptured germ cell cysts. Forcibly de-activate the chromatin increased primordial follicle formation, Therefore, the chromatin de-activation regulate the establishment of primordial follicles and their entry into quiescent states, offering potential strategies to improve ovarian reserve and egg production in different animals.

Keywords: chromatin de-activation; pre-granulosa cell; primordial follicle

DOI: https://doi.org/10.1016/j.jbc.2025.110598

Curr Opin Genet Dev. 2025 Aug 16. pii: S0959-437X(25)00087-5. [Epub ahead of print]94 102395

Genome instability in mammalian embryos implications for genome editing, development, and evolution.

Xiangyi Liu, Shuangyi Xu, Dieter Egli.

Genomic instability is a significant challenge in early mammalian development and a cause for developmental failure and abnormalities, particularly in humans. Here, we review our knowledge and explore its significance of genome instability in early embryos across multiple mammalian species, including humans, rhesus macaques, mice, bovines, equines, and porcine. All these species but mice share one feature: frequent chromosomal aberrations, aneuploidy, and developmental failure. We discuss the impact of genome instability on embryonic development, the applicability of gene editing using Cas9, and potential evolutionary implications. We also explore the role of germ cell and early embryo mutations and the bottleneck effect in mammals in comparison to lower vertebrates. Understanding genome stability in mammalian embryos can contribute to our understanding of genetic variation in development and evolution.

DOI: https://doi.org/10.1016/j.gde.2025.102395

Front Endocrinol (Lausanne). 2025 ;16 1613270

Novel direct effect of CCR2 receptor on follicle activation process.

Yamila Gamaleri, Delfina Sol Ferman, Alison Ting, Eduardo Raúl Dascal, Alejandro Lomniczi, Juan Pablo Jaworski, Marina Cinthia Peluffo.

Introduction: The regulation of primordial follicle activation is crucial for maintaining ovarian function, the duration of the reproductive phase, and fertility in women; therefore, we propose as our general objective to determine the physiological role of the chemokine receptor CCR2 within the follicular activation process.
Methods: Ovarian cortex fragments from adult domestic cats (Felis catus) were cultured under different experimental groups: control (media alone), CCR2 antagonist (1µM), and recombinant chemokine CC-motif ligand 2 (CCL2) at two concentrations (10 ng/ml and 100 ng/ml) for 4 h or 48 h. At the end of the culture, the fragments were collected for RNA extraction, cDNA synthesis, and quantitative real-time PCR (4 h) or fixed and processed for paraffin embedding (48 h) for hematoxylin and eosin staining or immunohistochemistry for Ki67, bromodeoxyuridine (BrdU) and AKTp.
Results: Stimulation of CCR2 significantly increased the normalized mRNA expression of KIT, FOXO3 (10 ng/ml), and AKT (100 ng/ml) compared to the control (p<0,05). Moreover, there was a significant increase in the percentage of transitional follicles (and a decrease in primordial follicles), together with an increase in oocyte diameter compared with the control and the antagonist groups (p<0.05). Also, in the presence of CCL2, a higher proportion of transitional and primary follicles immunolabeled for BrdU and Ki67 (p<0.05), as well as intense AKTp staining in the nucleus and cytoplasm of oocyte and granulosa cells of primordial, transitional and primary follicles, were observed. On the contrary, a lower proportion of BrdU and Ki67-positive follicles were observed in the antagonist group (p < 0,05).
Conclusion: Our results show a direct effect of the chemokine CCL2 and a role of the CCR2/CCL2 system on the ovarian cortex, suggesting that the CCR2 receptor signaling in the ovarian cortex may regulate events critical for promoting the stimulation of the transition from primordial to primary follicles.

Keywords: CCL2; CCR2; MCP-1; feline; follicle activation; folliculogenesis

DOI: https://doi.org/10.3389/fendo.2025.1613270