Biology subjects

Nikalayevich, E.

Publications and source records attributed to Nikalayevich, E..

4 recordsLinked to original sources

bioRxiv2026

Elevated cortical tension triggers precocious ectopic polarization in mammalian oocytes, associated with lower developmental potential.

Oocytes from many organisms polarize early during development, unlike mammalian oocytes. The significance of maintaining this homogeneous state in mammals remains unclear. We show that elevated cortical tension, via increased actomyosin contractility or disrupted cortical architecture, induces precocious cortical polarization mid-meiosis I, with an ectopic actomyosin-rich domain opposite the future division site. This polarization generates directional cytoplasmic flows that displace organelles and the spindle, accelerating its migration and disrupting its orientation. A hydrodynamic model coupling the polarized cortex to a viscous cytoplasm accounts for these rearrangements. Ectopic polarization persists in meiosis II and is associated with mislocalization of fertilization factors, increased fertilization rates and polyspermy, and reduced early embryonic development. A similar morphological signature arises spontaneously in subsets of mouse and human oocytes. These results reveal precocious cortical polarization as a previously unrecognized, mechanically accessible state largely absent from mammalian oocytes, which may contribute to variability in oocyte quality.

cell biology↗

bioRxiv2025

Elimination of separase inhibition reveals absence of cohesin protection in oocyte metaphase II

The meiotic segregation pattern to generate haploid gametes is mediated by step-wise cohesion removal by separase, first from chromosome arms in meiosis I, and then from the centromere region in meiosis II. In mammalian oocytes, separase is tightly controlled during the hours-long prometaphase and until chromosome segregation in meiosis I, activated for a short time window, and again inhibited until metaphase II arrest is lifted by fertilization. Centromeric cohesin is protected from cleavage by Sgo2-PP2A in meiosis I. It remained enigmatic how tight control of alternating separase activation and inactivation is achieved during the two divisions in oocytes. It was equally unknown when cohesin protection is put in place and removed. Using structure-function assays in knock-out mouse models we established the contributions of cyclin B1 and securin for separase inhibition during both divisions. When eliminating separase inhibition we found that cohesin is not protected early in meiosis I and at metaphase II arrest. Importantly, in meiosis II, the sole event required for cleavage of centromeric cohesin besides separase activation is prior kinetochore individualization in meiosis I.

cell biology↗

bioRxiv2022

An interpretable and versatile machine learning approach for oocyte phenotyping

Meiotic maturation is a crucial step of oocyte development allowing its potential fertilization and embryo development. Elucidating this process is important both for fundamental research and assisted reproductive technology. However, only few computational tools, based on non-invasive measurements, are currently available to characterize oocyte meiotic maturation. Here, we develop a computational framework to phenotype oocytes based on images or movies acquired exclusively in transmitted light. We first trained neural networks to segment the contours of oocytes and their zona pellucida using a diverse cohort of both mouse and human oocytes. We then defined a comprehensive set of morphological features to describe a single oocyte. We have implemented these steps in a versatile and user-friendly open source Fiji plugin available to the mouse and human oocyte community. Then, we present a machine learning pipeline based on selected features to automatically recognize oocyte populations and determine their morphological differences. Its first application is a novel approach to screen oocyte strains and automatically identify their morphological characteristics. We demonstrate its potential by phenotyping a well characterized genetically modified mouse oocyte strain. Its second application is to predict and characterize the maturation potential of oocytes. Importantly, we identify two new features to assess mouse oocyte maturation potential, consisting in the texture of the zona pellucida and the cytoplasmic particles size. Eventually, we tested whether these mouse oocyte quality features were applicable to human oocytes developmental potential.

bioinformatics↗

bioRxiv2021

Aurora B/C-dependent phosphorylation promotesRec8 cleavage in mammalian oocytes

To generate haploid gametes, cohesin is removed in a step-wise manner from chromosome arms in meiosis I and the centromere region in meiosis II, to segregate chromosomes and sister chromatids, respectively. Meiotic cohesin removal requires cleavage of the meiosis-specific kleisin subunit Rec8 by the protease Separase[1, 2]. In yeast, Rec8 is kept in a non-phosphorylated state by the action of PP2A-B56, which is localised to the centromere region, thereby preventing cohesin removal from this region in meiosis I[3-5]. However, it is unknown whether Rec8 has to be equally phosphorylated for cleavage, and whether centromeric cohesin protection is indeed brought about by dephosphorylation of Rec8 preventing cleavage, in mammalian meiosis. The identity of one or several potential Rec8-specific kinase(s) is also unknown. This is due to technical challenges, as Rec8 is poorly conserved preventing a direct translation of the knowledge gained from model systems such as yeast and C. elegans to mammals, and additionally, there is no turn-over of Rec8 after cohesion establishment, preventing phosphomutant analysis of functional Rec8. To address how Rec8 cleavage is brought about in mammals, we adapted a biosensor for Separase to study Rec8 cleavage in single mouse oocytes by live imaging, and identified phosphorylation sites promoting cleavage. We found that Rec8 cleavage by Separase depends on Aurora B/C kinase activity, and identified a residue promoting cleavage and being phosphorylated in an Aurora B/C kinase-dependent manner. Accordingly, inhibition of Aurora B/C kinase during meiotic maturation impairs endogenous Rec8 phosphorylation and chromosome segregation.

cell biology↗