Unravelling molecular signatures of oocyte developmental competence in cattle

Lead Research Organisation: Newcastle University
Department Name: Biosciences Institute

Abstract

Sustainable cattle production is critical to feed an increasing world population under projected food shortages due to climate change, and to alleviate methane emissions. Reproductive biotechnologies such as in vitro embryo production (IVEP) coupled with embryo transfer (ET) can increase the number of offspring from a single high genetic merit cow, contributing substantially to enhancing global food security, vastly decreasing the number of cows involved in cattle production systems, which in turn will reduce the carbon footprint of the cattle industry.
However, to achieve wider commercial acceptance, the efficiency of IVEP needs to be improved as only 15-40 % of oocytes used in IVEP manage to achieve an embryonic stage ready for ET. Aneuploidies (abnormal chromosome numbers) in fertilised eggs are overwhelmingly due to errors in female meiosis, and contribute significantly to implantation failure, spontaneous miscarriage and stillbirth. Studies in mice have highlighted the role of key proteins responsible for the prevention of aneuploidies in oocytes and other cell division errors that would ordinarily result in embryonic demise. Yet, there is a substantial knowledge gap in bovine oocytes in this regard. Hence, this project aims to elucidate the role of candidate proteins highly likely to provide a readout of oocyte developmental competence in cattle.
The project will utilise state-of-the-art live cell imaging where fluorescent transgenes will be microinjected into bovine oocytes to allow real time monitoring of proteins of interest, followed by analysis of known indicators of prognosis (e.g. spindle morphology and chromosome alignment to indicate genomic stability). Transgenic oocytes will also be fertilised and allowed to develop to the blastocyst stage (i.e. around 150 cells, a common embryonic stage used for ET) where several cellular and molecular endpoints associated embryo viability will be analysed (e.g. cell number and epigenetic markers such as H3K27me3). Importantly, no offspring will be produced (i.e. no ET will be performed) and abattoir-derived ovaries will be used to extract oocytes for the experiments (a by-product from the cattle industry), hence no animals will be culled for the sake of the project.
The project will provide the foundations to identify biomarkers of bovine oocyte developmental competence with the long-term aim of improving the efficient application of commercial bovine IVEP. Furthermore, given the similarities in oocyte and early embryo physiology between humans and cattle, this bovine model will provide data of relevance for human reproductive medicine.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T008695/1 01/10/2020 30/09/2028
2753060 Studentship BB/T008695/1 01/10/2022 30/09/2026