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

Abstract

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. The oviduct response to E2 is virtually unknown in an in vivo environment. 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 are differentially regulated by E2 and support gene expression changes that are required for normal embryo development and transport in mouse models.

Patterning of the female reproductive tract along antero-posterior and dorso-ventral axes is dependent on Amhr2+ mesenchyme in mice

“…Therefore, Rosa-DTA model used in our study uncovers new roles of Amhr2 + mesenchyme in patterning the epithelial lumen and promoting smooth muscle differentiation. Multiple single cell RNA transcriptomic studies have identified mesenchymal subpopulations and their specific markers in the developing and adult uterus (Kirkwood et al, 2021; Mucenski et al, 2019; Saatcioglu et al, 2019) and in the adult oviduct (Ford et al, 2021; McGlade et al, 2021). With the availabilities of Cre or CreER under the control of marker gene promoters, subpopulation-specific cellular ablation studies can be feasible and potentially provide insights into their specific functions.…”

Oviduct Epithelial Cells Constitute Distinct Lineages from the Ampulla to the Isthmus Related to High-Altitude Adaptation in Yak (Bos grunniens)

“…In this study, single-cell technique was adopted to analyze the heterogeneity, locus differentiation and ligand receptor pairs in the infundibulum, ampulla and isthmus of the oviduct in yaks. At present, there are few studies on the oviduct using single-cell technology, but some results demonstrate that E 2 shows differential expression in the transcription pro le of mouse oviduct ciliated cells and secretory cells [24], and there are differences in the differentiation of mouse epithelial cells at the distal and proximal end of the oviduct [25]. In the above studies, detailed researches on the three parts of the oviduct were not carried out.…”

“…In addition, insulin-like growth factor 1 (IGF1) was de ned as the target gene of the oviduct by mouse E 2 after single-cell RNA sequencing. Beyond that, E 2 can regulate epithelial, stromal, and muscle cells of the oviduct [24].…”