Estradiol and Progesterone Induced Differentiation and Increased Stemness Gene Expression of Human Fallopian Tube Epithelial Cells

Abstract

Fallopian tube epithelial cells (FTECs) are thought to be the origin of epithelial ovarian cancer. However, the effect of the hormones on FTECs is unknown, and therefore, this study explored this effect. We successfully derived FTECs from the fallopian tube epithelial layer and treated them with estradiol and progesterone. Reverse transcription polymerase chain reaction was used to evaluate the gene expression of the FTECs' hormone receptors. Confocal and electron microscopy were used to evaluate the morphology of the FTECs after they were treated with hormones. Finally, quantitative PCR was used to evaluate the gene expression of the hormone-treated FTECs. The results showed that the FTECs exhibited cuboidal cell morphology and could be maintained at a constant proliferation rate. Furthermore, flow cytometry revealed that the FTECs expressed stem cell markers, such as SSEA3, SSEA4, and Lgr5. Moreover, the FTECs could express both estrogen and progesterone receptors. In a culture treated with 400 nM estrogen, the FTECs differentiated toward ciliated cells, whereas in a culture treated with estradiol or progesterone, the FTECs increased their expression of certain stem cell markers (SSEA3, SSEA4, and Aldh1) and stemness genes [Wnt (AXIN2, LGR5, LGR6, and OLFM4) and Notch (Hes1) signaling]. In conclusion, hormones may alter the gene expressions of FTECs, and these cells may provide new insights into how FTECs regenerate in response to hormones.

Human fallopian tube epithelial cells exhibit stemness features, self-renewal capacity, and Wnt-related organoid formation

“…Yamamoto et al derived FTESC from fallopian tube epithelial cells (FTEC) and proposed the stem cell markers of FTEC as PAX8+, FOXJ1-, and PAX2- [12]; Wang et al found quiescent cell located at distal fallopian tube could be the origin of stem cells that could differentiate into different glandular cells [13]. Our previous study also showed expressions of stemness markers (SSEA3, SSEA4, and ALDH1) and stemness gene expressions (WNT and NOTCH signaling) in FTEC were affected by estradiol and progesterone [14].…”

Repeated hyperstimulation affects the ultrastructure of mouse fallopian tube epithelium

“…In mouse oviducts, CCs can be rise from NCs under the direction of ovarian steroids [ 67 , 68 ]. As recently seen in bovine, at least seven types of cells at different translational/transcriptional states of ciliogenesis are present in the oviductal epithelium, and their numbers are regulated by the estrous cycle [ 69 ].…”

Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

“…These cells were capable of generating clonally derived organoids that recapitulated the FT epithelial cell content and architecture [ 63 ]. Furthermore, transcript levels of these markers are upregulated by E2 or progesterone treatment in vitro, suggesting hormonal regulation of the stem cell phenotype [ 64 ]. Since fluid flows between intrauterine and pelvic compartments, we can postulate that the FT epithelium, which exists as a continuum of the endometrial luminal epithelium, may contribute to the regeneration of the endometrium and also give rise to ectopic endometriotic lesions through damage or shedding.…”