bims-cebooc 2026-03-29 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–03–29
seven papers selected by
Gabriele Zaffagnini, Universität zu Köln

Limitations of serial cloning in mammals.
Macrophages regulate meiotic initiation and germ cell clearance in the developing ovary.
Human stem cell-based embryo models: innovation, ethics, and policy.
Translational Fidelity Decline in the Aging Oocyte and Embryo Development.
Genetic and physical interactions reveal overlapping and distinct contributions to meiotic double-strand break formation in C. elegans.
Reprogramming the inactive X chromosome: dynamics and insights from the germline.
Structure and function of the synaptonemal complex.

Nat Commun. 2026 Mar 24. pii: 2495. [Epub ahead of print]17(1):

Limitations of serial cloning in mammals.

Sayaka Wakayama, Daiyu Ito, Rei Inoue, Masatoshi Ooga, Masaaki Toshishige, Yasunari Satoh, Hirosuke Shiura, Takashi Kohda, Arikuni Uchimura, Teruhiko Wakayama.

Mammals can now be cloned artificially, but it remains unknown whether they can also maintain their species through cloning. Herein, we continued serial cloning for 20 years from a single donor mouse. These re-cloned mice appeared normal and had normal lifespans, but large structural and lethal mutations accumulated in their DNA with each generation. The birth rate of serial cloning began to decline from the 27th generation, and the 58th generation was the last. When re-cloned mice from near the final generation were mated with males, their oocytes could be fertilized, but most embryos degenerated. However, a few embryos were normalized by meiosis and fertilization and developed to full term, suggesting that mammals rely on sexual rather than asexual reproduction to eliminate genetic anomalies caused by clonal reproduction.

DOI: https://doi.org/10.1038/s41467-026-69765-7
bioRxiv. 2026 Mar 03. pii: 2026.02.28.708733. [Epub ahead of print]

Macrophages regulate meiotic initiation and germ cell clearance in the developing ovary.

Xiaowei Gu, Satoko Matsuyama, Shu-Yun Li, Tony DeFalco.

  Tissue-resident macrophages are increasingly recognized for their roles in promoting organogenesis, yet how macrophages are involved in fetal ovarian development remains unclear. In particular, little is known about ovarian macrophage ontogeny and how it relates to germ cell entry into meiosis and establishment of the oocyte reserve. Here we combine temporally-controlled lineage tracing of yolk-sac erythro-myeloid progenitors, fetal HSC-derived progenitors, and postnatal monocytes to map multi-wave seeding and remodeling of ovarian macrophages across fetal and early postnatal life. We identify three major resident subsets defined by MHCII and CSF1R that display distinct expansion kinetics and persistence, and we show that CCR2-dependent monocyte recruitment is required for efficient maturation of postnatal macrophage populations. Functionally, transient or sustained depletion of CSF1R+ fetal macrophages perturbs ovarian vascular growth and triggers precocious meiotic initiation without overt loss of germ cells, leading to persistent, premature meiotic progression. Extending macrophage depletion into late gestation disrupts perinatal physiological germ cell attrition despite rapid postnatal macrophage repopulation. Together, our findings establish ovarian macrophages as stage-specific regulators that couple immune ontogeny to ovarian morphogenesis and germ cell quality control during establishment of the oocyte reserve.

Keywords:  germ cell; macrophage; macrophage ontogeny; meiotic initiation; monocyte; oocyte; oocyte reserve; ovarian development; ovarian follicle; ovary

DOI:  https://doi.org/10.64898/2026.02.28.708733
Hum Reprod. 2026 Mar 24. pii: deag035. [Epub ahead of print]

Human stem cell-based embryo models: innovation, ethics, and policy.

Alfonso Martinez Arias, Nicolas Rivron, Shahragim Tajbakhsh, Josephine Johnston, Cantas Alev, Laure Bally-Cuif, Elvan Böke, Tommaso Cavazza, Emma Cave, David Cyranoski, Laurent David, Miguel A Esteban, Jianping Fu, Niels Geijsen, Nienke de Graeff, Jacob H Hanna, Nick Hopwood, Maneesha S Inamdar, Fredrik Lanner, Brigitte Leeners, Zhen Liu, Maitre Jean Leon, Gabriella Minchiotti, Naomi Moris, Megan Munsie, Kathy K Niakan, Olivier Pourquie, Vincent Pasque, Martin Pera, Yaojin Peng, Sophie Petropoulos, Sharad Ramanathan, Janet Rossant, Peter Rugg-Gunn, Mitinori Saitou, Karen Sermon, Jose Silva, Thorold Theunissen, Margherita Turco, John Wallingford, Hongmei Wang, Aryeh Warmflash, Jun Wu, Leqian Yu.

  The aim of this White Paper is to establish a foundational framework for research, technological development, and regulation in the emerging field of stem cell-based embryo models (SCBEMs). These models, generated from Pluripotent Stem Cells, are designed to recapitulate essential events in early stages of human development. They have the potential to illuminate the early stages of embryo development and implantation and hold promise as an avenue to address global health challenges, including infertility and pregnancy loss, congenital, neonatal and adult conditions, and the need for organ transplants. While SCBEMs are not a substitute for human embryos, their tractability for large-scale analysis and their abilities to model the earliest stages of embryonic development suggest that they will have a significant impact on reproductive biology and regenerative medicine. But SCBEMs do not just raise novel scientific questions; they pose ethical and legal questions that need to be addressed. The paper stems from a meeting of a core group of researchers that met at the Institut Pasteur in Paris in November 2024 and represents the views of an extended group that has worked to elaborate the documents as a consensus for the field. Here, we provide a framework to guide research in this new field. We do this by summarizing the state of the science, assessing current SCBEM research in relation to its primary future applications and addressing the need for continued ethical and regulatory oversight associated with this new field.

Keywords:   in vitro fertilization; SCBEMs; blastocyst; embryogenesis; ethics; gametes; gastrulation; human embryos; implantation; pluripotent stem cells

DOI:  https://doi.org/10.1093/humrep/deag035
Int J Mol Sci. 2026 Mar 12. pii: 2614. [Epub ahead of print]27(6):

Translational Fidelity Decline in the Aging Oocyte and Embryo Development.

Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Ioannis Papapanagiotou, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Christina Trakateli, Nana Kojo Koranteng, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis, Georgios Daskalakis.

  Female reproductive aging is associated with a progressive decline in oocyte competence and reduced success in assisted reproductive technologies. While chromosomal abnormalities, mitochondrial dysfunction, and DNA damage have been extensively studied, these mechanisms do not fully explain developmental arrest in chromosomally euploid embryos or the variability in embryo competence. Human oocytes enter a transcriptionally quiescent state during meiotic maturation and rely almost entirely on the regulated translation of stored maternal messenger RNAs to support fertilization and early embryonic development until zygotic genome activation. In this context, translational fidelity becomes a critical determinant of proteome integrity and cellular function. Age-related alterations affecting ribosomal RNA integrity, transfer RNA modification, aminoacylation accuracy, and translational regulatory networks may impair the precision, timing, and coordination of protein synthesis. These defects can disrupt essential processes such as spindle assembly, cytoskeletal organization, and early cleavage dynamics, ultimately compromising embryo viability despite chromosomal normality. In addition, the follicular microenvironment, including redox balance, metabolic support, and signaling pathways, plays a crucial upstream role in maintaining translational integrity. This review integrates mechanistic evidence from molecular, cellular, and developmental studies to propose that progressive decline in translational fidelity represents a fundamental and previously underrecognized driver of reproductive aging. Understanding translational control as a central regulator of oocyte competence may provide new insights into unexplained IVF failure and support the development of novel biomarkers and therapeutic strategies aimed at preserving reproductive potential.

Keywords:  assisted reproduction; embryo development; maternal mRNA; oocyte aging; ribosome fidelity; translational control

DOI:  https://doi.org/10.3390/ijms27062614
Elife. 2026 Mar 25. pii: RP96458. [Epub ahead of print]13

Genetic and physical interactions reveal overlapping and distinct contributions to meiotic double-strand break formation in C. elegans.

Marilina Raices, Fabiola Balmir, Nicola Silva, Wei Li, McKenzie K Grundy, Dane K Hoffman, Elisabeth Altendorfer, Carlos J Camacho, Kara A Bernstein, Monica P Colaiacovo, Judith L Yanowitz.

  Double-strand breaks (DSBs) are the most deleterious lesions experienced by our genome. Yet, DSBs are intentionally induced during gamete formation to promote the exchange of genetic material between homologous chromosomes. While the conserved topoisomerase-like enzyme Spo11 catalyzes DSBs, additional regulatory proteins-referred to as 'Spo11 accessory factors'-regulate the number, timing, and placement of DSBs during meiotic prophase, ensuring that SPO-11 does not wreak havoc on the genome. Despite the importance of the accessory factors, they are poorly conserved at the sequence level, suggesting that these factors may adopt unique functions in different species. In this work, we present a detailed analysis of the genetic and physical interactions between the DSB factors in the nematode Caenorhabditis elegans, providing new insights into conserved and novel functions of these proteins. This work shows that HIM-5 is the determinant of X-chromosome-specific crossovers and that its retention in the nucleus is dependent on DSB-1, the sole accessory factor that interacts with SPO-11. We further provide evidence that HIM-5 mediates interactions with the different accessory factors subgroups, providing insights into how components on the DNA loops may interact with the chromosome axis.

Keywords:  C. elegans; SPO-11; crossover; developmental biology; double-strand break; meiosis

DOI:  https://doi.org/10.7554/eLife.96458
Biochem Soc Trans. 2026 Mar 25. pii: BST20250549. [Epub ahead of print]54(3):

Reprogramming the inactive X chromosome: dynamics and insights from the germline.

Yolanda Moyano Rodriguez, Maud Borensztein.

  Germline reprogramming is an essential process that resets the epigenome prior to gamete formation. Primordial germ cells (PGCs), the progenitors of oocytes and spermatozoa, undergo extensive epigenetic remodelling during development, including genome-wide DNA demethylation, histone modification remodelling, and large-scale reorganisation of 3D genome architecture. In female mammals, an additional layer of epigenetic regulation occurs during PGC reprogramming: the reactivation of the inactive X chromosome, namely, X-chromosome reactivation (XCR). Female PGC precursors carry an inactive X chromosome to ensure dosage compensation prior to reprogramming. While X-chromosome inactivation has been extensively studied for decades, XCR has only more recently emerged as a focus of investigation, and its functional importance for germline development and reproduction remains unclear. XCR takes place along PGC differentiation, from early emergence to meiosis, and involves loss of the long non-coding RNA XIST/Xist coating, DNA demethylation at X-linked promoters, and re-expression of X-linked genes from the inactivated X. Sequential molecular events occurring during XCR have been characterised using both in vivo and in vitro approaches in a broad range of mammals from rodents to humans. In recent years, the emergence of low-input and single-cell omics technologies has substantially advanced our understanding of the inactive X-chromosome reactivation in the germline. In this review, we synthetise recent insights into XCR dynamics in mouse, human, and non-human primate PGCs. We discuss the remaining knowledge gaps and the future perspectives in the field of XCR and germline epigenetic reprogramming.

Keywords:  X-chromosome inactivation; dosage compensation; epigenetic reprogramming; methylation; monoallelic expression; primordial germ cells

DOI:  https://doi.org/10.1042/BST20250549
J Cell Biol. 2026 May 04. pii: e202511222. [Epub ahead of print]225(5):

Structure and function of the synaptonemal complex.

Brenda I Cesar, Yumi Kim.

A defining feature of meiosis is the synaptonemal complex (SC), a zipper-like protein structure that forms between homologous chromosomes to regulate their recombination and segregation. Historically viewed as an enigmatic electron-dense scaffold, the SC is now recognized as a dynamic signaling platform that coordinates key meiotic processes. Here, we review recent advances in understanding SC structure and function. We describe diverse complementary approaches that have expanded the catalog of SC components and their network of interactions within this architecture. We highlight striking conservation in structural organization and ancient molecular modules that couple SC structure to crossover regulation and further discuss how the SC implements feedback mechanisms controlling meiotic DNA break formation and repair capacity to ensure faithful chromosome segregation across generations.

DOI: https://doi.org/10.1083/jcb.202511222