TNF-α effect on human delivery onset by CB1/TRPV1 crosstalk: new insights into endocannabinoid molecular signaling in preterm vs. term labor. Analysis of the EC/EV pathway and predictive biomarkers for early diagnosis of preterm delivery

BACKGROUND: Endocannabinoids/endovanilloid (EC/EV) system and inflammation are recognized as key regulators of cell-signaling pathways in female reproduction. The knowledge of predictive biomarkers involved in preterm birth (PTB) represents an important goal to make an early diagnosis. The aim of the study was to investigate the role of EC/EV system and inflammation in human delivery, in placental samples from spontaneous deliveries. METHODS: We examined the expression of genes encoding for the components of EC/EV system (CB1, CB2, TRPV1, MAGL, FAAH, DAGL, NAPE-PLD) and for inflammatory cytokines (IL-6, TNF-α) with qRT-PCR techniques, in human placental samples from preterm delivery (at 30 and at 34 weeks) compared to term delivery (40 weeks, control group). RESULTS: We found a marked increase of CB1, anandamide, and inflammatory cytokines, mainly TNF-α, together with TRPV1 down-regulation in term delivery group, compared to preterm groups (P<0.05). CONCLUSIONS: Our findings highlighted the emergent pivotal role of the EC/EV system and inflammation in spontaneous term delivery and provided the framework for future studies that investigate the CB1/TRPV1 crosstalk in preterm birth. Particularly, we found a link between the stimulation of CB1 receptors and the antagonism of TRPV1 channels, that could be used in PTB prevention, through selected molecules.