Biology subjects

Brison, D.

Publications and source records attributed to Brison, D..

5 recordsLinked to original sources

bioRxiv2024

Interaction between gene expression and morphokinetic parameters in undisturbed human embryo culture

The clinical in vitro fertilisation (IVF) need for optimal culture conditions and improved selection of human embryos for transfer led to the development of time-lapse systems built into incubators to allow a stable, well-defined and undisturbed culture environment with continual monitoring of embryo development. Clinical data suggest that both undisturbed culture of embryos and selection algorithms based on time-lapse morphometric parameters can potentially improve embryo development and live birth rates. However, there remains a need to validate and understand the mechanisms underlying the potential benefits of the time-lapse technology in IVF. In this study, we compared the gene expression of human embryos grown in an undisturbed time-lapse system with a conventional incubator and showed that there is no fundamental difference in the developmental program of the undisturbed embryos, which provides important reassurance concerning the time-lapse technology. We then performed a network-based integrative analysis based on the undisturbed blastocyst transcriptomes and identified time-lapse parameter correlated genes. These showed cross talk with identified embryo development gene functional modules, suggesting potential molecular mechanisms underlying the clinical predictive capabilities of embryo time-lapse morphokinetic parameters for subsequent live birth. This study suggests methodologies for assessing the impact of additional predictive correlates of value for optimal embryo development and understanding their mechanisms of action.

developmental biology↗

bioRxiv2024

Effect of glucose concentration in culture medium on the human preimplantation embryo methylome

Study questionDoes glucose concentration in culture medium have an impact on the DNA methylome of the early human embryo? Summary answerGlucose concentration is associated with changes in gene expression, global DNA methylation, methylation levels at CpG islands and at key histone modifications in human blastocysts. What is known alreadyPreimplantation human embryos are highly sensitive to their local environment, and this may have long term implications for the health of the developing embryo, fetus and offspring. Glucose is a standard component of human embryo culture media, due to its importance as a nutrient. However, concentrations of glucose differ widely between different commercially available types. The present study was designed to determine whether changes in glucose concentration could influence global methylation and gene expression in the human preimplantation embryo. Study design, size, durationHuman embryos were cultured in clinically relevant concentrations of glucose and global DNA methylation analysis was performed. The effect of glucose concentration on the embryo epigenome, specifically DNA methylation, was analysed. Participants/materials, setting, methodsHuman embryos surplus to treatment requirements were donated with informed consent from several ART centres. Embryos were cultured to the blastocyst stage in Vitrolife G-TL medium, either at 0.9 mM or 3.5 mM glucose, separated via immunosurgery into Inner Cell Mass (ICM) and trophectoderm (TE) samples, and compared for both DNA methylation and gene expression. This allowed us to evaluate the association between DNA methylation and previously importantly identified biological pathways. Main results and the role of chanceThe concentration of glucose in human embryo culture medium was associated with changes in gene expression and global DNA methylation in both ICM and TE, and methylation levels at CpG islands and key histone modifications. These results are significant because glucose is a major nutrient metabolised by human embryos in culture, and yet we know relatively little of its downstream effects on the genome and epigenome. Wider implications of the findingsCommercially available embryo culture media with varying glucose levels have also been associated with altered fetal growth, birthweight and postnatal development of IVF offspring. Our findings may have important ramifications for potential clinical markers of embryo quality and pregnancy initiation, and improve understanding of the mechanisms underlying the impact of the early environment on the long term health of ART offspring. Study funding/competing interest(s)This work was funded by the National Council for Science and Technology of Mexico (CONACyT), an NIHR pre-doctoral fellowship (PCAF) to MM, the NIHR Local Comprehensive Research Network and NIHR Manchester Clinical Research Facility, the University of Manchester and Manchester University NHS Foundation Trust. None of the authors has any conflict of interest to declare.

developmental biology↗

bioRxiv2023

Deep learning pipeline reveals key moments in human embryonic development predictive of live birth in IVF

Demand for IVF treatment is growing, however success rates remain low partly due to difficulty in selecting the best embryo to be transferred. Current manual assessments are subjective and may not take advantage of the most informative moments in embryo development. Here, we apply convolutional neural networks (CNNs) to identify key windows in preimplantation human development that can be linked to embryo viability and are therefore suitable for the early grading of IVF embryos. We show how machine learning models trained at these developmental time-points can be used to refine overall embryo viability assessment. Exploiting the well-known capabilities of transfer learning, we illustrate the performance of CNN models for very limited data sets, paving the way for the use on a clinic-by-clinic basis, catering for local data heterogeneity.

developmental biology↗

bioRxiv2019

Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos

1.BackgroundMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking.\n\nResultsHere, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilization, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration - showing that while there are alterations in activity over the course of development to respond to physiological demand, the overall efficiency is unchanged.\n\nConclusionEFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the parameters of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study oocyte and embryo metabolism.

developmental biology↗

bioRxiv2018

Interactome comparison of human embryonic stem cell lines with the inner cell mass and trophectoderm

Human embryonic stem cells (hESCs) derived from the pluripotent Inner cell mass (ICM) of the blastocyst are fundamental tools for understanding human development, yet are not identical to their tissue of origin. To investigate this divergence we compared the transcriptomes of genetically paired ICM and trophectoderm (TE) samples with three hESC lines: MAN1, HUES3 and HUES7 at similar passage. We generated inferred interactome networks using transcriptomic data unique to the ICM or TE, and defined a hierarchy of modules (highly connected regions with shared function). We compared network properties and the modular hierarchy and show that the three hESCs had limited overlap with ICM specific transcriptome (6%-12%). However this overlap was enriched for network properties related to transcriptional activity in ICM (p=0.016); greatest in MAN1 compared to HUES3 (p=0.048) or HUES7 (p=0.012). The hierarchy of modules in the ICM interactome contained a greater proportion of MAN1 specific gene expression (46%) compared to HUES3 (28%) and HUES7 (25%) (p=9.0x10-4). These findings show that traditional methods based on transcriptome overlap are not sufficient to identify divergence of hESCs from ICM. Our approach also provides a valuable approach to the quantification of differences between hESC lines. And Manchester Academic Health Sciences Centre

developmental biology↗