A pre-menopausal single-cell atlas for ovarian drug discovery

Single-cell atlas efforts have reshaped the way we understand cells across the human body. Despite their power, they have not been effectively used to study ovarian biology in the context of other tissues, nor have they comprehensively incorporated healthy tissues from pre-menopausal donors. A focused pre-menopausal single-cell atlas could both advance our understanding of this life stage and support identification of ovarian gene targets for indications prevalent among younger demographics, such as fertility management. Here, we present an integrated resource of single-cell datasets from pre-menopausal women (PreMeno Atlas), comprising 511,365 cells from 14 tissues, including the ovary. This unified resource enables transcriptomic comparisons across cell types, tissues, and organs within the pre-menopausal context. Our analysis revealed distinct ovarian cell gene signatures, with theca and stromal cells exhibiting the most unique transcriptional profiles among ovarian cell types. We further leveraged the PreMeno Atlas to prioritize ovary-specific genes with potential druggability, particularly G-protein coupled receptors (GPCRs), identifying GPR78, ADRB3, GPR20, and GPR101 as candidate targets. Finally, we assessed species homology of ovarian cell marker genes using a harmonized mouse ovulation and spatial transcriptomics dataset. Collectively, this work establishes the PreMeno Atlas as a resource for ovarian biology research and contraceptive target discovery.