bims-cebooc 2025-11-09 papers

Nat Cell Biol. 2025 Nov 04.

Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes.

Yuanzhuo Zhou, Kohei Asai, Hirohisa Kyogoku, Tomoya S Kitajima.

Chromosome mis-segregation during meiosis in oocytes causes miscarriages and congenital diseases. Ageing-associated premature chromosome separation is a major cause of mis-segregation. Effective prevention of premature chromosome separation has not yet been achieved. Here we design protein-based artificial kinetochores that act as decoys to prevent premature chromosome separation. Designed artificial kinetochore-like decoys are submicroscale clusters of NDC80-NUF2-tethered protein particles that can establish a biorientation-like state by competing with chromosomal kinetochores for HURP-decorated microtubules. This competition reduces excessive bipolar microtubule pulling forces exerted on chromosomes, thereby effectively preventing premature chromosome separation during meiosis I and II in aged mouse oocytes. These effects suppress egg aneuploidy. This study provides a decoy strategy with biocompatible artificial kinetochores to prevent ageing-associated meiotic errors in oocytes.

DOI: https://doi.org/10.1038/s41556-025-01792-w

Nat Aging. 2025 Nov 03.

A versatile cohesion manipulation system probes female reproductive age-related egg aneuploidy.

Jiyeon Leem, Tom Lemonnier, Ani Khutsaidze, Lei Tian, Xiaojun Xing, Suxia Bai, Timothy Nottoli, Binyam Mogessie.

Female reproductive aging is accompanied by a sharp increase in egg aneuploidy rates. Premature loss of chromosome cohesion proteins and early separation of chromosomes are thought to cause high aneuploidy rates during maternal aging. However, because cohesion loss occurs gradually throughout a woman's reproductive lifespan, and because cytoskeletal defects alone can lead to chromosomal abnormalities, the main causes of the rapid rise in aneuploidy at older reproductive ages are still unclear. In this study, we created a versatile and tunable cohesion manipulation system that enables rapid, dose-dependent degradation of the meiotic cohesin REC8 in live mouse oocytes. By coupling this system with quantitative high-resolution live imaging, we directly observed cohesion protein behavior during meiosis and tested the longstanding threshold model of aneuploidy development. Our results show that premature sister chromatid separation sharply increases only when REC8 levels drop below a critical threshold, supporting the idea of a nonlinear, vulnerability-triggering cohesion limit. We also used our system to examine how other age-related issues, such as cytoskeletal disruption and partial centromere dysfunction, can exacerbate chromatid separation in the context of weakened cohesion. This work provides a tractable oocyte platform for modeling and dissecting the multifactorial mechanisms driving female reproductive age-related egg aneuploidy.

DOI: https://doi.org/10.1038/s43587-025-00997-w

Genetics. 2025 Nov 04. pii: iyaf239. [Epub ahead of print]

Dopamine production in the central nervous system is important for follicle survival and interacts with genetic background and a high sugar diet during Drosophila oogenesis.

Rodrigo Dutra Nunes, Daniela Drummond-Barbosa.

Unhealthy diets, obesity, and low fertility are associated in Drosophila and humans. We previously showed that a high sugar diet, but not obesity, reduces Drosophila female fertility owing to increased death of newly formed germline cysts and vitellogenic follicles. Drosophila strains carrying mutations in the yellow (y) and white (w) pigmentation genes are routinely used for investigating the effects of high sugar diets, but it has remained unclear how this genetic background interacts with high sugar. Here, we show that the loss of y function is responsible for the high sugar diet-induced death of early germline cysts and vitellogenic follicles previously observed in y w mutant females. Dopamine supplementation prevents follicle death in y mutants on a high sugar diet. Conversely, severe dopamine imbalance or lack of dopamine production in the central nervous system causes follicle death regardless of diet or genetic background, while early germline cyst survival does not depend on dopamine. Our findings are broadly relevant to our understanding of how the effects of unhealthy diets might differ depending on genetic factors and highlight a key connection between dopamine metabolism in the central nervous system and ovarian follicle survival.

Keywords: yellow ; dopamine; follicle death; germline; high sugar diet; oogenesis

DOI: https://doi.org/10.1093/genetics/iyaf239

Reprod Biomed Online. 2025 Jul 18. pii: S1472-6483(25)00372-4. [Epub ahead of print] 105165

Oocyte-mediated repair of sperm DNA fragmentation: a critical determinant of embryo viability.

Maria Luisa Pardiñas, Carlos de Celis, Julia Gil, David Ortega-Jaen, Angel Martin, Amparo Mercader, Maria Jose de Los Santos.

DNA repair capacity is a critical biological process for maintaining genomic integrity in cells. However, certain cells, such as spermatozoa, possess limited DNA repair ability and depend on the oocyte for this function during fertilization. Among the various types of DNA damage, single- and double-strand sperm DNA fragmentation has emerged as a key factor influencing embryo development and clinical outcomes. Improperly repaired DNA fragmentation can result in developmental delays, embryo arrest or chromosomal abnormalities. This review explores the capacity of the oocyte to repair sperm DNA damage, and how maternal age affects this critical function. Through a structured literature review, the mechanisms involved in oocyte-mediated DNA repair are described and their clinical implications are evaluated. Findings indicate that oocyte quality, which diminishes with age, significantly impacts the efficiency of DNA repair processes, thereby influencing embryo viability and pregnancy success. While younger oocytes can partially compensate for sperm DNA fragmentation, aging oocytes show reduced repair capacity, contributing to poor reproductive outcomes. These insights emphasize the need for novel reproductive strategies aimed at enhancing oocyte quality and repair efficiency.

Keywords: Advanced maternal age; Embryo development; Oocyte repair; Sperm DNA fragmentation

DOI: https://doi.org/10.1016/j.rbmo.2025.105165

Dev Cell. 2025 Nov 03. pii: S1534-5807(25)00605-7. [Epub ahead of print]60(21): 2843-2845

In vitro oogenesis breaks free of the ovary.

Jay W Zussman, Diana J Laird.

In this issue of Developmental Cell, Nosaka et al. differentiate mouse pluripotent stem cells to large germinal vesicle-stage oocyte-like cells in the absence of ovarian somatic cells. Their paradigm advances the field toward clinical translation and offers insights into oogonial cyst breakdown, X chromosome dynamics, and requirements for oocyte growth and meiotic resumption.

DOI: https://doi.org/10.1016/j.devcel.2025.09.020