Abstract
Successful pregnancy requires the establishment of a complex dialogue between the implanting embryo and the endometrium. Knowledge regarding molecular candidates involved in this early communication process is inadequate due to limited access to primary human endometrial epithelial cells (EEC). Since pseudo-pregnancy in rodents can be induced by mechanical scratching of an appropriately primed uterus, this study aimed to investigate the expression of mechanosensitive ion channels in EEC. Poking of EEC provoked a robust calcium influx and induced an increase in current densities, which could be blocked by an inhibitor of mechanosensitive ion channels. Interestingly, RNA expression studies showed high expression of PIEZO1 in EEC of mouse and human. Additional analysis provided further evidence for the functional expression of PIEZO1 since stimulation with Yoda1, a chemical agonist of PIEZO1, induced increases in intracellular calcium concentrations and current densities in EEC. Moreover, the ion channel profile of human endometrial organoids (EMO) was validated as a representative model for endometrial epithelial cells. Mechanical and chemical stimulation of EMO induced strong calcium responses supporting the hypothesis of mechanosensitive ion channel expression in endometrial epithelial cells. In conclusion, EEC and EMO functionally express the mechanosensitive PIEZO1 channel that could act as a potential target for the development of novel treatments to further improve successful implantation processes.
Highlights
Successful pregnancy requires the establishment of a complex dialogue between the implanting embryo and the endometrium
Induced a significant increase in calcium concentration in hEEC (% of responding cells ≤ 2). These results showed functional expression of TRPM7, while no functional expression was detected for TRPV2/V4 and TRPC1/C4/C6 in human endometrial epithelial cells, excluding the potential contribution of polymodal Transient Receptor Potential (TRP) channels in the mechanosensitivity of hEEC
Mechanical stimulation of EEC resulted in robust Ca2+ influxes, and transient increases in current densities, that were not detected in the absence of extracellular Ca2+ and could be blocked in the presence of GsMTx4, an inhibitor of mechanosensitive channels
Summary
Successful pregnancy requires the establishment of a complex dialogue between the implanting embryo and the endometrium. Since pseudo-pregnancy in rodents can be induced by mechanical scratching of an appropriately primed uterus, this study aimed to investigate the expression of mechanosensitive ion channels in EEC. Mechanical and chemical stimulation of EMO induced strong calcium responses supporting the hypothesis of mechanosensitive ion channel expression in endometrial epithelial cells. EEC and EMO functionally express the mechanosensitive PIEZO1 channel that could act as a potential target for the development of novel treatments to further improve successful implantation processes. This study aims to provide evidence for the endogenous expression of mechanosensitive ion channels in EEC of human and mouse. We evaluate the potential of EMO as a valid model for primary human EEC to investigate the embryo-uterine crosstalk by studying the functional expression of mechanosensitive ion channels
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
