bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–05–24
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln



  1. Nat Commun. 2026 May 18.
      Mitochondria are highly dynamic organelles, and their spatiotemporal organization is strictly regulated. While it has long been recognized that mitochondria in ovulated oocytes are concentrated in the spindle hemisphere, the mechanism remains unknown. Through live cell imaging and modeling, we have discovered that mitochondrial polarization in MII oocytes is achieved through two distinct mechanisms: (i) a mechanism in which mitochondria are transported by actin-driven cytoplasmic streaming that is delimited to the spindle hemisphere; (ii) an active, MYO19 dependent channeling mechanism that directs mitochondria from beneath the spindle to the polarized cortex bilaterally and perpendicular to the long axis of the MII spindle. This directionality in mitochondrial streaming patterns the ooplasm of the spindle hemisphere, creating mitochondria-rich and mitochondria-poor regions. These features explain the establishment of the polar gradient of mitochondria in MII oocytes and may provide new insight into the spatiotemporal organization of mitochondria in cells.
    DOI:  https://doi.org/10.1038/s41467-026-73192-z
  2. J Vis Exp. 2026 Apr 28.
      The ovarian reserve consists of the oocytes available to a female for reproduction and are found in primordial follicles, each containing one oocyte surrounded by several granulosa cells. The oocytes start out as primordial germ cells that form outside the gonad and migrate to the developing ovary during embryonic development. Once they reach the ovary, they become oogonia and divide by mitosis, with incomplete cytokinesis, forming clusters of interconnected cells called germ cell cysts. While in cysts, the cells enter meiosis and become oocytes. In the mouse, two days before birth, the cysts begin to break apart, and each oocyte is packaged into a primordial follicle. Only some of the oocytes survive during this process, the rest undergo apoptosis. The regulation of cyst breakdown and primordial follicle formation is only partially understood, and identifying the molecules involved is crucial to understanding this process. Whole mount immunostaining of developing mouse ovaries can be used to determine the localization of potential regulatory molecules and to assess effects on primordial follicle formation due to mutation or other molecular changes using oocyte and somatic cell markers. Ovaries are harvested from fetal or neonatal mice, fixed in formaldehyde, and blocked. The ovaries are then exposed to antibodies against a protein of interest, followed by secondary antibodies conjugated to a fluorescent tag that detect the primary antibodies. Finally, the ovaries are mounted and examined by confocal microscopy. This procedure can detect multiple proteins of interest and can be applied to other small tissues, such as fetal mouse testes.
    DOI:  https://doi.org/10.3791/69455
  3. EMBO J. 2026 May 21.
      Programmed degradation of maternal proteins is essential for the oocyte-to-embryo transition (OET). While pharmacological inhibition studies have established the importance of proteasomes in ovarian reserve maintenance, oocyte maturation and fertilization, the physiological impact of intrinsic proteasome insufficiency and underlying molecular mechanisms remain poorly understood. In mice, endolysosomal vesicular assemblies (ELVAs), specialized membraneless compartments composed of proteasomes, endolysosomes and autophagosomes, facilitate protein degradation during oocyte maturation and early embryogenesis. In this study, we generated mice with oocyte-specific deletion of the proteasomal core subunit Psma7, to investigate the physiological function of the 20S proteasome and its roles in ELVAs-mediated protein degradation. PSMA7-deficiency destabilized 20S proteasomes and disrupted translocation of ELVAs, leading to pronounced accumulation of ubiquitinated proteins in oocytes and zygotes. Consequently, maternal Psma7 deletion resulted in female infertility, manifested by impaired oocyte maturation and developmental arrest at one- to two-cell stage. Furthermore, we observed reduced proteasome abundance and dysfunction of ELVAs in aged oocytes, providing a mechanistic explanation for the decline in developmental competence associated with oocyte aging. Taken together, our findings elucidate the critical function of proteasome-regulated proteostasis within ELVAs in maintaining oocyte quality during OET and reproductive aging.
    DOI:  https://doi.org/10.1038/s44318-026-00813-0
  4. Adv Exp Med Biol. 2026 ;1509 87-106
      Successful mammalian fertilization, resulting in the formation of a diploid zygote from haploid gametes, requires a series of events that enable a sperm to reach and fuse with an oocyte. To become competent for fertilization, the sperm must first undergo capacitation, a process that is followed by the acrosome reaction. During the acrosome reaction, the acrosome, a membrane-bound organelle localized to the sperm head, fuses with the sperm's plasma membrane and releases proteolytic enzymes that allow the sperm to penetrate the zona pellucida, an extracellular matrix surrounding the oocyte. After traveling through the zona pellucida, the sperm recognizes, binds to, and fuses with the oocyte plasma membrane, or the oolemma. This process is mediated by surface receptors on both the sperm and the oocyte. Once fertilization occurs, the oocyte blocks polyspermy by preventing additional sperm from accessing the oocyte. The oocyte undergoes a cortical reaction, in which cortical granules fuse with the oolemma to release enzymes that modify the zona pellucida, rendering it impermeable to the sperm entry. At the oolemma, the sperm-oocyte-binding capacity is reduced, preventing further sperm attachment.
    Keywords:  Acrosome proteins; Acrosome reaction; Cortical reaction; Fertilization; Oolemma; Polyspermy block; Sperm–oocyte binding; Sperm–oocyte fusion; Zona pellucida
    DOI:  https://doi.org/10.1007/978-3-032-22637-2_4
  5. bioRxiv. 2026 May 06. pii: 2026.05.01.722309. [Epub ahead of print]
      Chromosome segregation fidelity during meiosis is critical for genome integrity, with aneuploidy causing infertility, miscarriages, and congenital anomalies. In the oocytes of many species, spindle assembly occurs in the absence of centrosomes that normally function as microtubule-organizing centers at the poles. Such acentrosomal spindles are believed to pose significant challenges for accurate chromosome segregation compared to centrosomal organized spindles. Previous work in Drosophila has shown that the chromosomal passenger complex (CPC) is required for acentrosomal spindle assembly. We found that heterochromatin protein-1 (HP1) plays a critical role in regulating CPC localization and spindle assembly. Furthermore, HP1 moves to the microtubules, where it has roles in building a functional spindle and interacts with the CPC to regulate chromosome biorientation. These results indicate that spindle assembly is mediated by multiple interactions between the CPC, HP1, and the chromosomes, and provide insights into the mechanisms that restricts spindle assembly to the chromosomes in Drosophila oocytes.
    DOI:  https://doi.org/10.64898/2026.05.01.722309
  6. FEBS Open Bio. 2026 May 19.
      RNA silencing pathways use small RNAs to guide sequence-specific repression of endogenous genes, mobile elements, and viruses. It has been 25 years since RNA interference (RNAi) was found in mouse oocytes and became the first identified small RNA pathway in mammals. Today, three distinct small RNA pathways are known to operate in mammalian oocytes-in addition to RNAi, there is the microRNA (miRNA) pathway and the PIWI-associated RNA (piRNA) pathway. These pathways differ mechanistically and functionally and their co-existence in the female germline evolved into different arrangements. This review aims to provide a basic introduction to mammalian RNA silencing pathways with a focus on mouse oocytes and key aspects of the pathways, which influence their biological roles in oocytes and zygotes, across mammals.
    Keywords:  RNAi; miRNA; oocyte; piRNA; retrotransposon; siRNA
    DOI:  https://doi.org/10.1002/2211-5463.70273
  7. bioRxiv. 2026 May 04. pii: 2026.04.30.721999. [Epub ahead of print]
      The union of two germ cells to form a zygote, and subsequent early embryo development, are marked by radical remodeling of virtually every major class of biomolecules as the specialized germline states give way to the rapid and active growth that marks early development. In recent years, advances in ultra-low input genome-wide methods have enabled systematic analyses of mRNA abundance, and of chromatin organization, throughout early development in a variety of model systems. Here, we extend these efforts to the study of RNA binding protein (RBP) function in early mouse embryos, adapting REMORA 1 - based on fusing an RNA-editing enzyme to an RBP of interest - for use in early embryos. We benchmark our approach for several well-studied RBPs, successfully recovering expected features of their RNA cargos, and assayed the RNA cargos for 17 RBPs of interest for early gene regulation. Analysis of changes in mRNA metabolism following knockdowns of the RBPs surveyed here allowed us to identify direct regulatory functions for a subset of RBPs in the early mammalian embryo, including an unanticipated role for the RNA export adaptor Alyref in control of 3' polyadenylation sites. Together, our data provide a proof of concept resource for systematically exploring RBP functions in mammalian embryogenesis.
    DOI:  https://doi.org/10.64898/2026.04.30.721999
  8. Nat Struct Mol Biol. 2026 May 22.
      At the onset of reproduction, oviparous animals synthesize large amounts of yolk in somatic tissues to provide lipids and other nutrients to their progeny. However, whether the yolk transports other molecules, such as RNAs with gene-regulatory functions, remains largely unexplored. Here, we biochemically purified the yolk granules in the nematode Caenorhabditis elegans and show they contain microRNAs (miRNAs). We provide evidence that the yolk transports miRNAs from the intestine of the mother to the embryos by the lipoprotein yolk receptor RME-2. These yolk-enriched miRNAs inherited by the embryos regulate the transcriptomes of developing larvae. Moreover, environmental stresses and maternal age modulate the transfer of yolk-enriched miRNAs, contributing to stress-resilience benefits to progeny. This discovery establishes an alternative paradigm in intergenerational gene regulation, where the gut-germline axis orchestrates the transmission of environmental cues through yolk-enriched miRNAs. Our work, thus, reveals a mechanism underlying the soma-to-germline transfer of epigenetic information in animals.
    DOI:  https://doi.org/10.1038/s41594-026-01816-5
  9. bioRxiv. 2026 May 10. pii: 2026.05.08.723602. [Epub ahead of print]
      In meiosis, crossovers between homologous chromosomes generate genetic diversity and are required for accurate chromosome segregation, ensuring fertility. In mammals, HEI10 is one of three pro-crossover RING-domain factors implicated in protein modification by ubiquitin and/or SUMO and characterised by their dynamic accumulation at future crossover sites. However, the molecular architecture and enzymatic activity of mammalian HEI10 have remained unknown. Here, we show that human HEI10 has E3-ubiquitin ligase activity that depends on its higher-order assembly. We report the crystal structure of the HEI10 core, revealing how a 29-nm rod-like tetramer is formed through head-to-head association of two coiled-coil dimers that results in clustering of four RING domains around the molecular centre. HEI10 tetramers self-assemble through RING, coiled-coil, and C-terminal interfaces into fibrous and spherical higher-order structures. Structure-guided mutants show that higher-order assembly is required for HEI10 to catalyse K63-linked ubiquitin chain formation in vitro , with the most active species likely corresponding to a loose, non-fibrous network of assembled HEI10 molecules. Arabidopsis thaliana HEI10 retains the tetrameric core and higher-order assembly behaviour, suggesting a conserved principle of HEI10 function.
    DOI:  https://doi.org/10.64898/2026.05.08.723602
  10. Methods Mol Biol. 2026 ;3000 235-250
      Long-term space missions expose astronauts to an altered gravitational field (microgravity) that significantly affects human physiology. Although it is critical to assess the effect of microgravity on female reproductive health, this aspect remains a poorly investigated one. To date, interest in the effects on the main ovary hormones (estrogens) has been in depth for its role in bone loss, while the impact of altered estrogen availability on fertility and ovarian function is unclear. The female reproductive apparatus depends on a finely tuned hormonal network involving the hypothalamic-pituitary-ovarian axis. At the heart of this system are the ovarian follicles, composed of granulosa and theca cells, which cooperate in the synthesis of steroid hormones in supporting oocyte maturation. Folliculogenesis and estrogen production are tightly regulated by gonadotropins-FSH and LH-which act on these two distinct cell types. Any disruption in this delicate endocrine cross talk may impair oocyte quality, ovulatory function, and overall reproductive health. New evidence suggests that microgravity may interfere with this delicate hormonal balance, potentially reducing estrogen synthesis and impairing follicular development mostly by downregulating aromatase activity. As the regulation of ovarian function is distributed across different tiers, investigation is particularly delicate. Nevertheless, molecular assessment of relevant parameters can be performed upon cells/tissues cultures growing in real and simulated weightlessness in order to collect data and drawing explicative models.
    Keywords:  Aromatase; Estrogens; Female fertility; Microgravity; Ovarian biology; Steroidogenesis
    DOI:  https://doi.org/10.1007/978-1-0716-5174-2_11