The link between mitochondrial dysfunction and epigenetic alterations in metabolically compromised oocytes: a key pathway to subfertility and a target to improve embryo quality and offspring health. 01/11/2020 - 31/10/2024

Abstract

Maternal metabolic disorders, e.g. obesity, affect millions worldwide and are known to cause subfertility. Altered ovarian micro-environment and the direct impact on oocyte quality is a key factor in this pathogenesis. The oocyte undergoes dynamic epigenetic reprogramming during normal follicular development. Timely acquisition of epigenetic modifications is critical for genomic imprinting and regulation of transcription during subsequent development. Dysregulated oocytes carry persistent epigenetic defects that harm offspring health. Recent insights from somatic cells and cancer biology show that mitochondria are the machinery by which metabolic changes can translate into epigenetic (dys)regulation. This is due to altered bioenergetics or changed availability of intermediate products needed for the establishment of epigenetic marks. We learned that mitochondrial dysfunction is a main cause of reduced oocyte quality under metabolic stress. Fundamental understanding of the mitochondrial-nuclear communication in growing oocytes is lacking but crucial for the development of efficient interventions to improve oocyte quality and fertility and for the protection of embryo quality and offspring health. We aim to examine the direct link between mitochondrial dysfunction in growing oocytes and epigenetic alterations, to study if these alterations are preventable or reversible using mitochondrial targeted treatments, and to test the impact of these treatments on the offspring's health.

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  • Research Project