Cyclic exposure of the endometrium to ovarian sex steroids during the menstrual cycle induces a transition between proliferative and receptive states involving a different variety of cell types (ie, epithelial, stromal, endothelial, and immune cells) in preparation for embryo implantation during the narrow window of implantation. The study of the female reproductive system cells across these different phases contributes to our understanding of the healthy endometrium at the cellular level, supporting comparisons with pathological conditions, such as endometriosis, endometrial cancer, or Asherman's syndrome. Single-cell RNA sequencing technology represents a powerful tool that can discern the gene expression profiles of each cell within a tissue sample and has recently revealed the complex collaborations taking place between diverse cell types during the distinct endometrial phases. This review aims to summarize those studies that have employed single-cell RNA sequencing to deepen our understanding of the endometrium at single-cell resolution during the menstrual cycle. We discuss the transitions taken by distinct cell populations across the proliferative and secretory phases and the general importance of these transitions to successful embryo implantation. Furthermore, we analyze the use of single-cell RNA sequencing technology to study in vitro models of healthy endometrium and endometrial carcinoma. We believe that future studies using single-cell RNA sequencing will be essential to understanding the behavior of the endometrium as a whole and identifying potential avenues for the improved management of endometrial diseases.

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