Published 02 May 2019
With formalities now completed, ESHRE can report that a submission on actin-dependent chromosome cohesion in oocytes took the €50,000 award, while a far-reaching project on the effects of obesity on embryo metabolism - and the potential for correction in culture media - was selected for the €150,000 award.
The principal grant - worth €150,000 and on the broad subject of 'maternal determinants of embryo developmental ability' - was awarded to the group of Roger Sturmey at the University of Hull and Hull York Medical School, UK, working with Dr Adam Stevens and Professor Daniel Brison at the University of Manchester, on a project whose aims are first to establish the extent of the biochemical and gene network effects of obesity in embryos, and second - if evident - to explore the possibility of correction through the modified composition of culture media. Such results, said Sturmey, are 'urgently needed' with an ever growing prevalence of obesity in the population of fertility patients. The project, formally titled 'Embryo quality revisited: understanding and treating the hidden impact of maternal obesity', was finally selected from 71 original submissions.
Speaking to Focus on Reproduction, Sturmey, who is presently the Basic Science Officer of ESHRE's SIG Embryology, said the project would be developed by two neighbouring institutions: first to provide the supernumerary embryos and clinical data of a regular IVF centre, and second the biochemical analysis necessary for a detailed phenotype of blastocysts derived from overweight and obese women. Sturmey's lab in Hull, which continues the distinguished work of Henry Leese in the metabolic determinants of embryo viability, will measure and compare the consumption of oxygen, glucose, pyruvate, lactate and amino acid and the metabolism of triglyceride in the blastocysts of overweight and normal weight subjects. The background data for much of this work has already been developed and validated in the Hull lab. The impacts of disrupted metabolism will be studied at the gene level using advanced biological network analysis developed in Manchester by Stevens.
While the biochemical results of the project present the possibility of a scientifically based biomarker for embryo viability, its intriguing prospect is the opportunity for correction through the adaptation of culture medium. 'The work will provide proof-of-principle that culture medium modifications can restore embryo phenotype,' said Sturmey, 'and will provide a significant step towards assessing the clinical utility of a precision medicine approach in ART.'
The project was originally scheduled to run over 18 months and Sturmey now hopes it can begin soon into 2019. 'The award means that we'll be able to appoint a talented post-doctoral fellow for some really fundamental research, while providing a great individual development opportunity to work with human embryos,' he said. 'Appointing the right person can take time, but we hope to be in a position to make an appointment in the Spring. Ultimately, I think it's possible that we can demonstrate the principle that correction of any obesity-linked adaptation of the embryo can be reversed. The proof of principle will indicate that modifying the culture environment can have positive benefits when measured using a range of endpoints.
'In terms of routine treatment,' added Sturmey, 'this EHSRE-supported work will start the journey, but there will be significant follow-up before we can say with confidence that we can produce a culture system tailored to an individual setting and suitable for safe use in the clinic.'
The award of €50,000 to Binyam Mogessie at the University of Bristol, UK, will support a project investigating the contribution of the protein actin to chromosome cohesion pathways in a mouse model. These pathways, says Mogessie, hold oocyte centromeres together before chromosome segregation and loss of cohesion may therefore explain the effect of age on aneuploidy. The specifics of the study will be to develop high-resolution imaging assays to detect nanometric changes in centromere distance and dissect actin-dependent centromeric cohesion in living oocytes using localised and acute protein degradation tools. 'Ultimately,' says Mogessie, 'and by extending centromeric actin enrichment experiments to human oocytes of older patients, it may be possible to test whether inter-centromere distance in aged oocytes can be altered for better chromosome segregation outcomes.'
The Research Grant Committee of ESHRE, which is responsible for final selection, congratulates Binyam Mogessie and Roger Sturmey in making these two winning proposals. Projects were selected based on scientific excellence, originality and feasibility, and these criteria were met by these and many others of the 111 submissions.