bims-cebooc 2026-02-01 papers

Issue of 2026–02–01
five papers selected by
Gabriele Zaffagnini, Universität zu Köln

Nature. 2026 Jan 28.

Robust cytoplasmic partitioning by solving a cytoskeletal instability.

Melissa Rinaldin, Alison Kickuth, Adam Lamson, Benjamin Dalton, Yitong Xu, Pavel Mejstřík, Stefano Di Talia, Jan Brugués.

Early development across vertebrates and insects critically relies on robustly reorganizing the cytoplasm of fertilized eggs into individualized cells1,2. This intricate process is orchestrated by large microtubule structures that traverse the embryo, partitioning the cytoplasm into physically distinct and stable compartments3,4. Here, despite the robustness of embryonic development, we uncover an intrinsic instability in cytoplasmic partitioning driven by the microtubule cytoskeleton. By combining experiments in cytoplasmic extract and in vivo, we reveal that embryos circumvent this instability through two distinct mechanisms: either by matching the cell-cycle duration to the time needed for the instability to unfold or by limiting microtubule nucleation. These regulatory mechanisms give rise to two possible strategies to fill the cytoplasm, which we experimentally demonstrate in zebrafish and Drosophila embryos, respectively. In zebrafish embryos, unstable microtubule waves fill the geometry of the entire embryo from the first division. Conversely, in Drosophila embryos, stable microtubule asters resulting from reduced microtubule nucleation gradually fill the cytoplasm throughout multiple divisions. Our results indicate that the temporal control of microtubule dynamics could have driven the evolutionary emergence of species-specific mechanisms for effective cytoplasmic organization. Furthermore, our study unveils a fundamental synergy between physical instabilities and biological clocks, uncovering universal strategies for rapid, robust and efficient spatial ordering in biological systems.

DOI: https://doi.org/10.1038/s41586-025-10023-z

EMBO J. 2026 Jan 26.

TORC1-dependent translation drives chromatin remodeling during the germ-cell-to-maternal transition in Drosophila.

Noor M Kotb, Gulay Ulukaya, Anupriya Ramamoorthy, Lina Seojin Park, Julia Tang, Dan Hasson, Prashanth Rangan.

Proper oogenesis requires a programmed transition from an undifferentiated germ-cell gene expression program to a maternal gene-expression state. While this process depends on the heterochromatin-mediated silencing of germ-cell genes, the upstream mechanisms that enforce this transcriptional shift remain unclear. Here, we uncover a translation-driven chromatin remodeling program that promotes oocyte fate in Drosophila. Through a loss of function screen, we identify TORC1 activity (Mio, Raptor), ribosome biogenesis (Zfrp8, Bystin, Aramis), and a translation factor (eEF1α1) as essential for silencing the germ-cell program. We show that TORC1 activity increases during oocyte specification, and that disruption of TORC1 activity, translation, or ribosome biogenesis during this window impairs heterochromatin maintenance at germ-cell gene loci. Polysome profiling reveals that Zfrp8 promotes translation of the nuclear pore component Nucleoporin 44A (Nup44A), whose function is independently required for chromatin organization and repression of a cohort of germ-cell genes. Taken together, our findings reveal that a transient increase in translation orchestrates chromatin remodeling to ensure commitment to oocyte fate.

Keywords: Chromatin; Oocyte; Ribosome; TORC1; Translation

DOI: https://doi.org/10.1038/s44318-026-00697-0

Biol Reprod. 2026 Jan 30. pii: ioag030. [Epub ahead of print]

High-fat and choline-deficient western diets disrupt the ovarian microenvironment in mice†.

César A Pinzón-Osorio, Camila L Moreira, Ines L Assis, Larissa S Magalhães, Bianka M Zanini, Jéssica D Hense, Driele N Garcia, Juliane B Prosczek, Giulia C Perreira, Pedro H da Cruz, Rodrigo A Vaucher, Tiago V Collares, Bernardo G Gasperin, Michael B Stout, Miguel A Brieño-Enríquez, Augusto Schneider.

Obesity and metabolic dysfunction induced by high-fat and Western-style diets are key contributors to reproductive aging. However, the specific contributions of diet-induced obesity and liver damage to ovarian aging and follicle depletion remain unclear. This study investigated the impact of a high-fat diet (HFD) and a choline-deficient Western diet (CDWD) on ovarian aging in two mouse strains. Three-month-old female mice (C57BL/6 and Swiss) were assigned to a control standard diet (CSD), choline-deficient control diet (CDC), HFD, or CDWD for ten weeks. C57BL/6 mice fed an HFD exhibited significant body mass gain, intra-abdominal fat accumulation, and insulin resistance, whereas Swiss mice did not develop obesity. Both strains developed hepatomegaly and steatohepatitis under CDWD in the absence of obesity, as expected for this choline-deficient diet. HFD and CDWD increased serum cholesterol and high-density lipoprotein levels in both strains. The ovarian follicle reserve was unaffected by diet or strain, despite a modest increase in follicular atresia in HFD-fed C57BL/6 mice. However, both HFD and CDWD promoted macrophage infiltration, lipofuscin accumulation, stromal fibrosis, and increased stromal proliferative activity. These findings demonstrate that metabolic stress from HFD and CDWD remodels the ovarian microenvironment and induces early hallmarks of ovarian aging independent of follicle depletion. Metabolic responses were strain-dependent; however, both obesity-driven metabolic dysfunction and obesity-independent liver injury led to similar ovarian microenvironment remodeling. This highlights a previously underappreciated pathway linking metabolic diseases to reproductive decline and suggests that ovarian microenvironmental remodeling is an early sign of ovarian aging in response to diet-induced metabolic stress.

Keywords: Senescence; fertility; fibrosis; masld; obesity; ovary

DOI: https://doi.org/10.1093/biolre/ioag030

Biomolecules. 2025 Dec 23. pii: 22. [Epub ahead of print]16(1):

The Xenopus Oocyte System: Molecular Dynamics of Maturation, Fertilization, and Post-Ovulatory Fate.

Ken-Ichi Sato.

The Xenopus oocyte has long served as a versatile and powerful model for dissecting the molecular underpinnings of reproductive and developmental processes. Its large size, manipulability, and well-characterized cell cycle states have enabled generations of researchers to illuminate key aspects of oocyte maturation, fertilization, and early embryogenesis. This review provides an integrated overview of the cellular and molecular events that define the Xenopus oocyte's transition from meiotic arrest to embryonic activation-or alternatively, to programmed demise if fertilization fails. We begin by exploring the architectural and biochemical landscape of the oocyte, including polarity, cytoskeletal organization, and nuclear dynamics. The regulatory networks governing meiotic resumption are then examined, with a focus on MPF (Cdk1/Cyclin B), MAPK cascades, and translational control via CPEB-mediated cytoplasmic polyadenylation. Fertilization is highlighted as a calcium-dependent trigger for oocyte activation. During fertilization in vertebrates, sperm-delivered phospholipase C zeta (PLCζ) is a key activator of Ca2+ signaling in mammals. In contrast, amphibian species such as Xenopus lack a PLCZ1 ortholog and instead appear to rely on alternative protease-mediated signaling mechanisms, including the uroplakin III-Src tyrosine kinase pathway and matrix metalloproteinase (MMP)-2 activity, to achieve egg activation. The review also addresses the molecular fate of unfertilized eggs, comparing apoptotic and necrotic mechanisms and their relevance to reproductive health. Finally, we discuss recent innovations in Xenopus-based technologies such as mRNA microinjection, genome editing, and in vitro ovulation systems, which are opening new avenues in developmental biology and translational medicine. By integrating classic findings with emerging frontiers, this review underscores the continued value of the Xenopus model in elucidating the fundamental processes of life's origin. We conclude with perspectives on unresolved questions and future directions in oocyte and early embryonic research.

Keywords: MAPK signaling; MPF (maturation-promoting factor); Xenopus oocyte; calcium wave; cytoplasmic determinants; developmental competence; fertilization and egg activation; oocyte atresia

DOI: https://doi.org/10.3390/biom16010022

Nat Protoc. 2026 Jan 26.

Putting mammalian early embryonic cells into dormancy.

Dhanur P Iyer, Heidar Heidari Khoei, Nicolas Rivron, Aydan Bulut-Karslioglu.

Mammalian development starts at fertilization and continually progresses until birth, except in cases in which an interruption is favorable to the embryo and the mother. Many mammals have the ability to pause development in case of suboptimal resources or routinely as part of their reproductive cycle-a phenomenon called 'embryonic diapause'. Diapause can be mimicked in vivo in mice via surgical removal of the ovaries or hormone injections. This procedure is laborious and invasive, ruling out its use across species. We have developed in vitro protocols through which mouse blastocysts, human blastoids and pluripotent stem cells from both species can be induced to enter a diapause-like dormant state via pharmacological inhibition of mTOR. Here, we describe in detail how embryos, blastoids and stem cells can be transitioned into and out of dormancy under different culture conditions. We further explain critical parameters to ensure success and propose experimental readouts. These in vitro embryonic dormancy setups can be used to uncover molecular mechanisms of dormancy, to test environmental or pharmacological effectors and to further innovate culture systems for species in which in vitro reproductive technologies are limited. We anticipate that researchers with ~1 year of embryo- and stem cell-handling experience should be able to achieve consistent results and evaluate outcomes. Altogether, inducing dormancy in vitro offers the possibility to slow down embryonic development for exploratory investigations of molecular mechanisms and eventually to expand the time window before implantation for clinical assays.

DOI: https://doi.org/10.1038/s41596-025-01303-z