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![EMO as a model for human endometrial epithelial cells. (a) mRNA expression levels of selected ion channels in primary hEEC (light blue), early (P2) (blue) and late (P8) (dark blue) passage EMO, and the endometrial epithelial cell line HEC-1A (orange). mRNA levels were relatively quantified to the geometric mean of the housekeeping genes HPRT1 and PGK1 and represented as mean ± SEM. n = 4 (hEEC), n = 3 (EMO). *p < 0.05, **p < 0.01 compared to the hEEC condition with Two-way Anova and Dunnett’s multiple comparison test; Nd = not detectable. (b–g) Ca²⁺ microfluorimetry. Representative trace of ratiometric Ca²⁺ imaging (Fura2) on EMO (b) and HEC-1A (c). Cells were subjected to a series of mechanical stimuli by pressing a glass probe onto the cell surface for 100 ms (N ≥ 10 independent experiments). (d) Time course of Ca²⁺ experiments in which a hypotonic solution (HTS; 210 mOSm) was added to either EMO or HEC-1A cells at the indicated time point. Ionomycin (Iono; 2 µM) was applied as a positive control. Shown is the mean trace ± SEM. The corresponding mean amplitude of [Ca²⁺]I upon application of HTS in either 2 mM extracellular Ca²⁺ or in the presence of GsMTx4 (20 µM) is shown in (e). ***p < 0.001 using the non-parametric Kruskal-Wallis test corrected with Dunn’s multiple comparisons. n = 3 experiments with a total minimum of 200 cells. (f) Time course of intracellular Ca²⁺ in EMO and HEC-1A upon stimulation with Yoda1 (5 µM). Ionomycin (Iono; 2 µM) was applied as a positive control. Shown is the mean trace ± SEM. (g) represents the mean amplitude of [Ca²⁺]I upon application of Yoda1, trypsin or mibefradil (mib) in either hEEC, early passage EMO, late passage EMO or HEC-1A cells. *p < 0.05, **p < 0.01, ***p < 0.001 using the non-parametric Kruskal-Wallis test corrected with Dunn’s multiple comparisons compared to the hEEC conditions. n = 3 experiments with a total minimum of 80 cells. nt = not tested.](publication/331020123/figure/fig5/AS:959313518538776@1605729574734/EMO-as-a-model-for-human-endometrial-epithelial-cells-a-mRNA-expression-levels-of.png)
EMO as a model for human endometrial epithelial cells. (a) mRNA expression levels of selected ion channels in primary hEEC (light blue), early (P2) (blue) and late (P8) (dark blue) passage EMO, and the endometrial epithelial cell line HEC-1A (orange). mRNA levels were relatively quantified to the geometric mean of the housekeeping genes HPRT1 and PGK1 and represented as mean ± SEM. n = 4 (hEEC), n = 3 (EMO). *p < 0.05, **p < 0.01 compared to the hEEC condition with Two-way Anova and Dunnett’s multiple comparison test; Nd = not detectable. (b–g) Ca²⁺ microfluorimetry. Representative trace of ratiometric Ca²⁺ imaging (Fura2) on EMO (b) and HEC-1A (c). Cells were subjected to a series of mechanical stimuli by pressing a glass probe onto the cell surface for 100 ms (N ≥ 10 independent experiments). (d) Time course of Ca²⁺ experiments in which a hypotonic solution (HTS; 210 mOSm) was added to either EMO or HEC-1A cells at the indicated time point. Ionomycin (Iono; 2 µM) was applied as a positive control. Shown is the mean trace ± SEM. The corresponding mean amplitude of [Ca²⁺]I upon application of HTS in either 2 mM extracellular Ca²⁺ or in the presence of GsMTx4 (20 µM) is shown in (e). ***p < 0.001 using the non-parametric Kruskal-Wallis test corrected with Dunn’s multiple comparisons. n = 3 experiments with a total minimum of 200 cells. (f) Time course of intracellular Ca²⁺ in EMO and HEC-1A upon stimulation with Yoda1 (5 µM). Ionomycin (Iono; 2 µM) was applied as a positive control. Shown is the mean trace ± SEM. (g) represents the mean amplitude of [Ca²⁺]I upon application of Yoda1, trypsin or mibefradil (mib) in either hEEC, early passage EMO, late passage EMO or HEC-1A cells. *p < 0.05, **p < 0.01, ***p < 0.001 using the non-parametric Kruskal-Wallis test corrected with Dunn’s multiple comparisons compared to the hEEC conditions. n = 3 experiments with a total minimum of 80 cells. nt = not tested.
Source publication
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 me...
Citations
... Inhibition of BMP (Noggin) and TGF-β/Alk (A83-01) pathways was crucial, alongside EGF, FGF10, 17βestradiol (E2), insulin (ITS), and inhibition of p38 MAPK, ROCK, and sirtuin. Hormone treatment replicated the menstrual cycle and early decidualization (Haider et al., 2019;Hennes et al., 2019;Bui et al., 2020;Cochrane et al., 2020;Syed et al., 2020). Trophoblast organoids were derived with minimal differences in medium. ...
The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.
... Mechanoreceptors, whose signaling is modified under microgravity, are important for embryo implantation and dysfunctional mechanoreceptors may be involved in pregnancy complications, such as preeclampsia 131,132 . In summary, endometrium and reproductive immunology including maternal immune tolerance are understudied areas in space biology. ...
As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female reproductive system. The effects of spaceflight on human reproductive potential, fertility, implantation and subsequent pregnancy resulting in a healthy live birth must be considered before planning prolonged spaceflight missions and the colonization of planets. In this review, we explore what is known and what remains to be learned about the effects of space travel on female reproductive endocrinology. We also delve deeper into reproductive endocrinology and discuss normal physiologic mechanisms at the molecular level to have a better understanding of how it may change during spaceflight. The rigors of spaceflight including radiation, gravitational stressors, and circadian rhythm changes could potentially affect ovulation, fertilization, endometrial receptivity, preimplantation embryo development, embryo implantation, placentation, and pregnancy. Thus, we will examine what is known about spaceflight effects on the hypothalamic–pituitary–gonadal (HPG) axis, ovarian folliculogenesis and steroidogenesis, early embryogenesis, endometrial receptivity, and pregnancy. We further discuss the recent advances in reproductive endocrinology and future research platforms. Establishing a better understanding of the effect of space travel on female reproductive health, as well as developing countermeasures to mitigate adverse effects, are decisive components of our species’ successful transition to an interplanetary one.
... More recently a second inwardly rectifying mechano-gated channel, Piezo1, which is preferential to Ca under physiological conditions was identified in myometrium (Barnett et al., 2022) and endometrium (Hennes et al., 2019). Stimulation of Piezo1 in human myometrial strips ex vivo using a Piezo 1 agonist, Yoda1, caused relaxation of oxytocin-induced contractions (Barnett et al., 2022). ...
Multiple pregnancy remains a relatively common occurrence, but it is associated with increased risks of adverse outcomes for the mother and her babies and presents unique challenges to healthcare providers. This review will briefly discuss multiple pregnancies, their aetiology and their problems, including preterm birth, before reviewing the processes leading to normal labour onset and how they may be different in a multiple pregnancy. The mechanisms by which mechanical factors i.e., uterine distension or ‘stretch’ contribute to uterine excitability and the timing of labour onset will be the major focus, and how over distention may pre-dispose multiple pregnancies to preterm birth. This includes current thinking around the role of mechano (stretch) sensitive ion channels in the myometrium and changes to other important regulators of excitability and contraction which have been identified from studies using in vitro and in vivo models of uterine stretch. Physiological stimuli arising from the fetus(es) and placenta(s) will also be discussed. In reviewing what we know about the myometrium in multiple pregnancy in humans, the focus will be on twin pregnancy as it is the most common type of multiple pregnancy and has been the most studied.
... The calcium measurements were performed as previously described [21]. Absolute calcium concentrations were calculated from the ratio of the fluorescence signals at both wavelengths (F340/F380) after correction for the individual background fluorescence signals, using the Grynkiewicz Equation [22]: for which the calibration constants R 0 , R 1 and K eff were determined as followed: R 0 defines the ratio in Ca 2+ free medium supplemented with 10 mM EGTA, whereas R 1 comprises the ratio in high Ca 2+ medium (10 mM). ...
... Next, the expression levels for these genes were further examined over different stages of the human cycle ( Fig. 7F and G), and although F2RL1 remained constantly expressed, epithelial cells in early secretory stage showed the highest levels. [15,21]. RNAscope experiments using cells in 2D culture derived from hEMO and intact 3D organoids revealed a positive signal for the presence of F2RL1 and co-expression with the epithelial marker CDH1 (E-cadherin) (Fig. 8A). ...
... However, a detailed investigation of the signaling pathway in primary culture of mEEC was never shown before. The positive effect of shear stress on the [Ca 2+ ] I oscillations could potentially be explained by the functional expression of mechanosensitive ion channels in primary endometrial epithelial cells, like PIEZO1 [21]. The co-application of shear stress and trypsin, potentiated the percentage of oscillating cells, which could be explained by a combined effect of mechanosensitive channels and PAR2. ...
Background:
Early embryo implantation is a complex phenomenon characterized by the presence of an implantation-competent blastocyst and a receptive endometrium. Embryo development and endometrial receptivity must be synchronized and an adequate two-way dialogue between them is necessary for maternal recognition and implantation. Proteases have been described as blastocyst-secreted proteins involved in the hatching process and early implantation events. These enzymes stimulate intracellular calcium signaling pathways in endometrial epithelial cells (EEC). However, the exact molecular players underlying protease-induced calcium signaling, the subsequent downstream signaling pathways and the biological impact of its activation remain elusive.
Methods:
To identify gene expression of the receptors and ion channels of interest in human and mouse endometrial epithelial cells, RNA sequencing, RT-qPCR and in situ hybridization experiments were conducted. Calcium microfluorimetric experiments were performed to study their functional expression.
Results:
We showed that trypsin evoked intracellular calcium oscillations in EEC of mouse and human, and identified the protease-activated receptor 2 (PAR2) as the molecular entity initiating protease-induced calcium responses in EEC. In addition, this study unraveled the molecular players involved in the downstream signaling of PAR2 by showing that depletion and re-filling of intracellular calcium stores occurs via PLC, IP3R and the STIM1/Orai1 complex. Finally, in vitro experiments in the presence of a specific PAR2 agonist evoked an upregulation of the 'Window of implantation' markers in human endometrial epithelial cells.
Conclusions:
These findings provide new insights into the blastocyst-derived protease signaling and allocate a key role for PAR2 as maternal sensor for signals released by the developing blastocyst.
... With the change in hormonal treatment, EEOs established by Luddi et al. demonstrated the distinct features of corresponding phases of the menstrual cycle in terms of both morphology and function. [37] Significantly, EEOs in the mid-secretory phase displayed the luminal cell surface with large protrusions named pinopodes, which is one of the critical markers of the implantation window. The expression of genes related to endometrial receptivity including progestagen associated endometrial protein (PAEP), vascular endothelial growth factor, insulin like growth factor 1 and matrix metallopeptidase 26 increased in EEOs of the mid-secretory phase compared to the proliferative phase, making them suitable indicators of the implantation window. ...
... Furthermore, based on the prior knowledge that mechanosensitive ion channels participate in interactions between the endometrium and the blastocyst, expression of the PIEZO1 channel was described in endometrial organoids and primary endometrial epithelial cells. [37] Strong calcium responses were observed in EEOs under chemical and mechanical stimulation, which provided further evidence for the functional expression of mechanosensitive PIEZO1 channels in endometrial epithelial cells. Consequently, the role of the PIEZO1 channel in maternal-fetal crosstalk at the implantation interface was validated. ...
A coordinated crosstalk between the maternal body and embryo is indispensable in a successful pregnancy. However, reliable models to study the potential cellular and molecular mechanisms of maternal-fetal interaction have not been established. The widely used research models including animal models and cell lines have significant limitations. Recently, the emergence and advancement of organoids have aroused attention. Endometrial organoids and trophoblast organoids which recapitulate human decidua and trophoblasts in three-dimensional cultures provide new opportunities to study the physiological or pathological processes of decidualization and implantation. Furthermore, to recapitulate precise cell-cell communication in the decidual microenvironment in vivo, the co-culture of multicellular organoids will be a potential optimal model for future investigations of crosstalk at the maternal-fetal interface. Here, we focus on the latest development and advancement of endometrial organoids and trophoblast organoids.
... Preadipocytes were seeded in six well-plates and induced to differentiate into adipocytes in standard adipogenic media alone, as previously described by our group (31), in the presence of the PIEZO1 agonist Yoda1 10 µM (Tocris, Cat N°5586), a concentration reported in different cell types (18,29,(33)(34)(35)(36). Adipogenesis was evaluated using Bodipy 493/503 (ThermoFisher Cat N°D3922), a neutral lipid staining, and the nuclear stain NucSpot ® Live 650 (Biotium, Cat N°40082) and reported as Bodipy fluorescence intensity/nuclei count using long-term live-cell imaging IncuCyte ® S3 system. ...
... As expected, the expression of Piezo1 was essential to enhance Ca2+ influx in preadipocytes ( Figure 2). This observation coincides with those in dental pulp stem cells (DP-MSC) (33), adipocytes (18), and endometrial epithelial cells (35), where Ca 2+ fluxes shifts are essential to induce mechanoreceptor responses. ...
During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT’s anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [si Piezo1 ; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in si Piezo1 cells but not in NC; in contrast, si Piezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.
... Piezo1 was first identified in astrocytes in the mid-2000s (Satoh et al., 2006), and is the subject of the 2021 Nobel Prize in Physiology or Medicine. It has since been found in other tissues (John et al., 2018;Li et al., 2014), including human endometrium (Hennes et al., 2019), where its aberrant expression is thought to contribute to preeclampsia (Arishe et al., 2020). Importantly, until now Piezo1 has not been characterized in human myometrium. ...
Approximately 10% of US births deliver preterm before 37 weeks of completed gestation. Premature infants are at risk for life‐long debilitating morbidities and death, and spontaneous preterm labour explains 50% of preterm births. In all cases existing treatments are ineffective, and none are FDA approved. The mechanisms that initiate preterm labour are not well understood but may result from dysfunctional regulation of quiescence mechanisms. Human pregnancy is accompanied by large increases in blood flow, and the uterus must enlarge by orders of magnitude to accommodate the growing fetus. This mechanical strain suggests that stretch‐activated channels may constitute a mechanism to explain gestational quiescence. Here we identify for the first time that Piezo1, a mechanosensitive cation channel, is present in the uterine smooth muscle and microvascular endothelium of pregnant myometrium. Piezo is downregulated during preterm labour, and stimulation of myometrial Piezo1 in an organ bath with the agonist Yoda1 relaxes the tissue in a dose‐dependent fashion. Further, stimulation of Piezo1 while inhibiting protein kinase A, AKT, or endothelial nitric oxide synthase mutes the negative inotropic effects of Piezo1 activation, intimating that actions on the myocyte and endothelial nitric oxide signalling contribute to Piezo1‐mediated contractile dynamics. Taken together, these data highlight the importance of stretch‐activated channels in pregnancy maintenance and parturition, and identify Piezo1 as a tocolytic target of interest. image
Key points
Spontaneous preterm labour is a serious obstetric dilemma without a known cause or effective treatments.
Piezo1 is a stretch‐activated channel important to muscle contractile dynamics.
Piezo1 is present in the myometrium and is dysregulated in women who experience preterm labour.
Activation of Piezo1 by the agonist Yoda1 relaxes the myometrium in a dose‐dependent fashion, indicating that Piezo1 modulation may have therapeutic benefits to treat preterm labour.
... Studies have shown that PIEZO1-mediated Ca 2+ influx can activate NFAT in cells such as osteoblasts 79 , but this has yet to be verified in immune cells. PIEZO1 expression is particularly abundant in mechano-active tissues such as the lungs, bladder and skin 80 , and PIEZO1 is transcriptionally expressed across a wide range of immune cell subsets, whereas TRPV4 expression appears more limited to a few myeloid subsets 81 . ...
Immune responses are governed by signals from the tissue microenvironment, and in addition to biochemical signals, mechanical cues and forces arising from the tissue, its extracellular matrix and its constituent cells shape immune cell function. Indeed, changes in biophysical properties of tissue alter the mechanical signals experienced by cells in many disease conditions, in inflammatory states and in the context of ageing. These mechanical cues are converted into biochemical signals through the process of mechanotransduction, and multiple pathways of mechanotransduction have been identified in immune cells. Such pathways impact important cellular functions including cell activation, cytokine production, metabolism, proliferation and trafficking. Changes in tissue mechanics may also represent a new form of ‘danger signal’ that alerts the innate and adaptive immune systems to the possibility of injury or infection. Tissue mechanics can change temporally during an infection or inflammatory response, offering a novel layer of dynamic immune regulation. Here, we review the emerging field of mechanoimmunology, focusing on how mechanical cues at the scale of the tissue environment regulate immune cell behaviours to initiate, propagate and resolve the immune response. This Review considers how the biophysical properties of a tissue are able to shape immune cell function through the process of mechanotransduction. There are multiple mechanotransduction pathways that operate in immune cells and the authors highlight these and the emerging field of mechanoimmunology.
... In the gastrointestinal tract epithelium, the functional role of Piezo1 channel is currently under investigation [10]. In the female reproductive system, Piezo1 channel has been detected in endometrial epithelial cells and their activation was shown to stimulate a robust Ca 2+ influx [11]. However, the expression and function of the Piezo1 channel in the male reproductive system, especially in the epididymis, remains elusive. ...
... Considering the preference for Ca 2+ of Piezo1 channel in response to mechanical stimuli in various tissue and cells [11,17,18], the hydrostatic pressure and the rhythmic contraction activity characteristic of the epididymal duct [19,20], it is possible that Piezo1 channels participate in the regulation of transepithelial K + secretion via KCa channels in the rat epididymal epithelium. The present study, therefore, aimed to investigated the functional expression of the Piezo1 channel in the rat epididymal epithelium and uncovered its potential role in the regulation of transepithelial K + secretion. ...
... As has been previously reported, the physiological and pathological processes mediated by Piezo1 channels primarily involve mechanical and chemical stimulation induced Ca 2+ responses [11,34,35]. In this study, we also found that the activation of Piezo1 channel stimulated a robust Ca 2+ influx in rat epididymal epithelial cells. ...
The Piezo1 channel, a mechanosensitive channel that exhibit a preference for Ca²⁺, play multifarious physiological and pathological roles in the endothelium and epithelium of various tissues. However, the functional expression of Piezo1 channel in the epithelium of the male reproductive tract remains unknown. In the present study, the expression of Piezo1 channel in the rat epididymis was determined by real-time quantitative PCR, western blot and immunohistochemical analysis. Our data revealed that Piezo1 channels were located in the epithelial layer of the rat epididymis, with higher expression levels in the corpus and cauda regions. The pro-secretion function of Piezo1 channel was then investigated using short circuit current (ISC) and intracellular Ca²⁺ imaging techniques. Application of Yoda1, a selective Piezo1 channel activator, stimulated a remarkable decrease in the ISC of the epididymal epithelium. Pharmacological experiments revealed that the ISC response induced by Piezo1 channel activation was abolished by pretreating epithelial cells with the Yoda1 analogue, Dooku1, the selective mechanosensitive cation channel blocker, GsMTx4, or removal of basolateral K⁺. Meanwhile, we demonstrated that activation of Piezo1 channel triggered a robust Ca²⁺ influx in epididymal epithelial cells. The possible involvement of Ca²⁺- activated K⁺ channels (KCa) in transepithelial K⁺ secretion was then evaluated. And that big conductance KCa (BK), but not small conductance or intermediate conductance KCa, mediated Piezo1-elicited transepithelial K⁺ secretion. Moreover, we demonstrated that NKCC and NKA were responsible for supplying substrate K⁺ during transepithelial K⁺ secretion. These data demonstrate that the activation of Piezo1 channel promotes BK-mediated transepithelial K⁺ secretion, and thus may plays an important role in the formation of a high K⁺ concentration in epididymal intraluminal fluid.
... Indeed, it was shown that Na + influx via TRPM4 results in a decreased Ca 2+ influx in many different cell types, including various immune and cancer cells [49,[56][57][58]. Our results showing high expression of TRPM4 in EEC are in line with earlier reports, illustrating high TRPM4 expression in both human and mouse EEC [18,59]. Interestingly, expression of TRPM4 was significantly decreased after EMT induction, suggesting a strong association with the epithelial cell phenotype. ...
Transient receptor potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP mRNA expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasticity is essential for normal functioning. However, it is unknown whether TRP channel mRNA expression is subject to the phenotypic switching that occurs during epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), and whether TRP channel mRNA expression is associated with aggressive phenotypes in endometrial cancer (EC). Here, we induced EMT and MET in vitro using in primary EEC and ESC, respectively, and analyzed expression and functionality of TRP channels using RT-qPCR and intracellular Ca ²⁺ imaging. The outcome of these experiments showed a strong association between TRPV2 and TRPC1 mRNA expression and the mesenchymal phenotype, whereas TRPM4 mRNA expression correlated with the epithelial phenotype. In line herewith, increased TRPV2 and TRPC1 mRNA expression levels were observed in both primary and metastatic EC biopsies and in primary EC cells with a high EMT status, indicating an association with an aggressive tumor phenotype. Remarkably, TRPV2 mRNA expression in primary EC biopsies was associated with tumor invasiveness and cancer stage. In contrast, increased TRPM4 mRNA expression was observed in EC biopsies with a low EMT status and less aggressive tumor phenotypes. Taken together, this dataset proved for the first time that TRP channel mRNA expression is strongly linked to cellular phenotypes of the endometrium, and that phenotypic transitions caused by either experimental manipulation or malignancy could alter this expression in a predictable manner. These results implicate that TRP channels are viable biomarkers to identify high-risk EC, and potential targets for EC treatment.
