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

Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

* This study is supported by National Institutes of Health (NIH), National Institute of Environmental Health Sciences awards number 1ZIAES103311 to FJD and 1ZIAES070065 to KSK, the Eunice Kennedy Shriver National Institute of Child Health & Human Development awards number R01HD042311 to JPL, R01HD097087 to WW, R01HD097087-01S1 to GGH, R01HD097087-02S1 to EAM, R00HD096057 to DM, PDEP Award from the Burroughs Wellcome Fund to DM, and Louis Stokes Alliance for Minority Participation (LSAMP) Research Award to KKS.