The evolution of ovarian somatic cells characterized by transcriptome and chromatin accessibility across rodents, monkeys and humans

Abstract The ovary plays a crucial role in the reproductive system of female mammals by producing mature oocytes through folliculogenesis. Non-human model organisms are extensively utilized in research on human ovarian biology, thus necessitating the investigation of conservation and divergence molecular mechanisms across species. In this study, we employed integrative single-cell analysis of transcriptome and chromatin accessibility to identify the evolutionary conservation and divergence patterns of ovaries among humans, monkeys, mice, rats, and rabbits. Our analyses based on scRNA-seq and scATAC-seq data revealed that theca cells exhibited the most significant changes during evolution. Furthermore, by conducting joint analyses of scRNA-seq and scATAC-seq data, we discovered a common cis-regulatory architecture in theca cells across species. These findings have potential implications for biomedical and genetic research in non-human organisms as they can be used to validate observations made in humans. Additionally, our investigation into non-coding genomic regions led us to identify intergenic highly transcribed regions (igHTRs) that may contribute to the evolution of species-specific phenotypic traits. Overall, our study provides valuable insights into understanding the molecular characteristics of adult ovaries while offering new perspectives for studying human ovarian physiology and diseases.