bims-mazytr 2025-07-27 papers

Issue of 2025–07–27
five papers selected by
川一刀

Nat Cell Biol. 2025 Jul 22.

Metabolic regulation of key developmental events during mammalian embryogenesis.

Metabolic regulation is critical in embryonic development and influences key processes such as fertilization, zygotic genome activation, cell compaction, implantation, gastrulation and organ development. Here we explore the interplay between metabolism and embryonic development in the context of important sequential key embryonic events, highlighting the orchestration of developmental processes by various metabolites and signalling molecules. Key metabolites, including glucose, fatty acids and amino acids, act as modulators of developmental processes, while also serving as energy sources and building blocks for cellular structures. Understanding the intricate relationship between metabolism and embryogenesis may provide insights into developmental disorders and potential therapeutic interventions.

DOI: https://doi.org/10.1038/s41556-025-01720-y

Biochem Soc Trans. 2025 Jul 22. pii: BST20240469. [Epub ahead of print]

Advances in mechanochemical modelling of vertebrate gastrulation.

Alex M Plum, Mattia Serra, Cornelis J Weijer.

Gastrulation is an essential process in the early embryonic development of all higher animals. During gastrulation, the three embryonic germ layers, the ectoderm, mesoderm and endoderm, form and move to their correct positions in the developing embryo. This process requires the integration of cell division, differentiation and movement of thousands of cells. These cell behaviours are coordinated through shortand long-range signalling and must involve feedback to execute gastrulation in a reproducible and robust manner. Mechanosensitive signalling pathways and processes are being uncovered, revealing that shortand long-range mechanical stresses integrate cell behaviours at the tissue and organism scale. Because the interactions between cell behaviours, signalling and feedback are complex, combining experimental and modelling approaches is necessary to elucidate the regulatory mechanisms that drive development. We highlight how recent experimental and theoretical studies provided key insights into mechanical feedback that coordinates relevant cell behaviours at the organism scale during gastrulation. We outline advances in modelling the mechanochemical processes controlling primitive streak formation in the early avian embryo and discuss future developments.

Keywords: biological models; biophysics; computational biology; developmental biology; systems biology

DOI: https://doi.org/10.1042/BST20240469

Microsc Microanal. 2025 Jul 15. pii: ozaf037. [Epub ahead of print]31(4):

Leucine-Rich Repeat Kinase 2 Regulates Mitochondria for Zygotic Genome Activation in Mouse Early Embryos.

Yu-Lan Lu, Zi-Yu Wei, Xiao-Ting Yu, Li-Zhou Qin, Lin-Lin Hu, Shao-Chen Sun, Shang-Lin Yang.

Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein known for its involvement in neurodegenerative disorders, particularly Parkinson's disease, where it is considered one of the most common genetic contributors. LRRK2 plays multiple roles in cellular signaling, protein trafficking, and cytoskeletal dynamics. In present study, using mouse as the mammalian model, we reported its important roles in early embryo development. We showed that LRRK2 accumulated around nucleus before two-cell stage but distributed in the cytoplasm of blastomeres after four-cell stage. Loss of LRRK2 activity induced two-cell to four-cell transition defects, indicating the failure of zygotic genome activation during embryo development. We showed the mitochondria dysfunction after LRRK2 inhibition, since the mitochondria distribution, intensity, ATP production, and mitochondria number were all altered. This might further induce the evaluated ROS level for the occurrence of oxidative stress. Besides, we also observed that the cortex and cytoplasmic actin in the blastomere of embryos were decreased, which further linked with mitochondria. In summary, we showed that LRRK2 activity is essential for actin-based mitochondria distribution and function, which further controls the occurrence of oxidative stress for mouse early embryo development.

Keywords: Parkinson’s disease; actin; mitochondria; oocyte; oxidative stress

DOI: https://doi.org/10.1093/mam/ozaf037

Sci Rep. 2025 Jul 18. 15(1): 26163

Regulation of autophagy and its role in late preimplantation during mouse embryo development.

Kei Uechi, Itsuki Koide, Saya Kanie, Tadashi Yamazaki, Satoshi Kishigami.

Autophagy is a system that contributes to cellular homeostasis by degrading intracellular proteins and organelles. Autophagy is essential for the preimplantation development of mammalian embryos, lack of which results in developmental arrest at the 4/8-cell stages. The role of autophagy beyond the compaction stage remains insufficiently explored. In this study, we investigated the role of autophagy after the 4/8-cell stages in mice using chloroquine (CQ), an autophagy inhibitor. CQ treatment from the 4/8-cell to morula stage impaired development, reducing the number of Cdx2-positive cells, an effect rescued by amino acid (AA) supplementation. CQ treatment also downregulated TFAP2C, an upstream regulator of Cdx2,which was similarly restored by AA supplementation. Consistently, autophagy at this stage showed higher activity in the outer cells and lower activity in the inner cells of the embryo. Treatment with XMU-MP-1, an MST1/2 inhibitor targeting the Hippo signaling pathway, disrupted this spatial regulation by inducing autophagy in the inner cells. Stage-specific staining revealed temporal and positional regulation of autophagy activity. These findings illustrate that autophagy during the morula stage promotes differentiation into the trophectoderm by supplying AAs, a process regulated by the Hippo signaling pathway.

Keywords: Autophagy; Embryonic development; Hippo signaling; Preimplantation; Trophectoderm differentiation

DOI: https://doi.org/10.1038/s41598-025-11359-2

Front Bioeng Biotechnol. 2025 ;13 1610539

3D visualization of uterus and ovary: tissue clearing techniques and biomedical applications.

Qiqi Liu, Zhuo Song, Simin Liu, Zirui Dong, Xi Zheng, Tak Yeung Leung, Xiaoyan Chen.

Recent advancements in tissue clearing and three-dimensional (3D) visualization technologies have enabled subcellular-level examination of entire organs, particularly in complex structures such as the ovary and uterus. Traditional histological approaches are limited by two-dimensional views, which restrict our understanding of female reproductive system functions. In this review, we highlight the innovations in 3D tissue clearing techniques applied to uterine and ovarian tissues, which, combined with analytical tools, facilitate comprehensive 3D visualization and image analysis. We evaluate the advantages and disadvantages of three primary categories of tissue clearing techniques: organic solvent-based, hydrogel-based, and hydrogel-embedded methods, specifically regarding the uterus and ovary. Light-sheet and multiphoton microscopy complement these techniques, providing unprecedented capabilities for high-resolution imaging of large tissue volumes. Tissue clearing technologies provide a robust strategy for early diagnosis of uterine and ovarian pathologies. Additionally, we explore the integration of tissue clearing technologies with spatial transcriptomics and AI-driven analytical tools to achieve comprehensive 3D molecular mapping. We hope this review contributes to a better understanding of tissue clearing techniques and can help researchers in navigating methodological choices for uterine and ovarian investigations.

Keywords: 3D visualization; AI; ovary; spatial omics; tissue clearing; uterus

DOI: https://doi.org/10.3389/fbioe.2025.1610539