The Healthy Reproductive Ageing (HERA) Study (360G-Wellcome-302536_Z_23_Z)

Reproductive health in women is under-researched and the field lacks key experimental tools and resources to advance biological understanding. Human genetic approaches have identified many determinants of reproductive ageing and disease risk, however extracting mechanistic insight from these findings has been challenging given the inaccessibility of ovarian tissue across different developmental stages. To address this, the HERA study will integrate human genetic approaches with functional studies in model systems. We will use multi-omics to annotate the regulatory landscape of the human genome across ovarian development and ageing. Genome-wide functional CRISPR screens with relevant cellular models will identify genes influencing ovarian phenotypes. These data will be integrated with our human omics datasets to identify high confidence targets for further characterization in in vivo mouse models. Our functional models will address two important phenotypes: reproductive ageing and ovary-centric disease. This synergistic approach, bringing together lead researchers and collaborators across multiple disciplines, will overcome some of the long-standing limitations in studying the ovary. We will provide the scientific and clinical community with new and much-needed tools and resources, accessed via our HERA knowledge portal. Our findings will inform future therapeutic approaches to preserve fertility and treat ovary-centric disorders.