Cell-type specific analysis of physiological action of estrogen in mouse oviducts

One of the endogenous estrogens, 17β-estradiol (E₂ ) is a female steroid hormone secreted from the ovary. It is well established that E₂ causes biochemical and histological changes in the uterus. However, it is not completely understood how E₂ regulates the oviductal environment in vivo. In this study, we assessed the effect of E₂ on each oviductal cell type, using an ovariectomized-hormone-replacement mouse model, single-cell RNA-sequencing (scRNA-seq), in situ hybridization, and cell-type-specific deletion in mice. We found that each cell type in the oviduct responded to E₂ distinctively, especially ciliated and secretory epithelial cells. The treatment of exogenous E₂ did not drastically alter the transcriptomic profile from that of endogenous E₂ produced during estrus. Moreover, we have identified and validated genes of interest in our datasets that may be used as cell- and region-specific markers in the oviduct. Insulin-like growth factor 1 (Igf1) was characterized as an E₂ -target gene in the mouse oviduct and was also expressed in human fallopian tubes. Deletion of Igf1 in progesterone receptor (Pgr)-expressing cells resulted in female subfertility, partially due to an embryo developmental defect and embryo retention within the oviduct. In summary, we have shown that oviductal cell types, including epithelial, stromal, and muscle cells, are differentially regulated by E₂ and support gene expression changes, such as growth factors that are required for normal embryo development and transport in mouse models. Furthermore, we have identified cell-specific and region-specific gene markers for targeted studies and functional analysis in vivo.