Endocannabinoid system from maternal-fetal interface is involved in preterm birth induced by LPS

MARVALDI, CAROLINA; SCHANDER, JULIETA AYLEN; AISEMBERG, JULIETA; FRANCHI, ANA MARIA; WOLFSON, MANUEL LUIS

Buenos Aires

Simposio; International Symposium on Reproductive Health: overcoming barriers for research in reproduction; 2021

Centro de Estudios Farmacológicos y Botánicos (CEFyBO) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA)

Preterm birth (PTB) is the leading cause of mortality and morbidity in neonates. It is well known that premature deliveries are mainly associated with infectious processes and the stability of the maternal-fetal interface is essential for the maintenance of pregnancy. The endocannabinoid system (ECs) is one of several signaling pathways involved in different aspects of the physiopathology of reproduction. The present study aimed to investigate the participation of ECs in the maternal-fetal interface, using an LPS-induced preterm labor model. Our group developed a murine model of preterm labor, induced by two injections of LPS on day 15 of pregnancy, that produces an 85% of PTB in Balb/C mice. Using this model, we observed in deciduas from LPS treated mice a decrease in CB1 receptor protein level vs control deciduas (p < 0.05). Conversely, CB1 receptor protein levels increased in PBMC after LPS treatment. Regarding the enzyme that synthesizes AEA, (N-acylphosphatidylethanolamine-specific phospholipase D, NAPE-PLD), we observed that its protein levels were diminished in both, deciduas and PBMC, from LPS treated mice. On the other hand, the enzyme that degrades AEA (fatty acid amide hydrolase, FAAH) protein levels and activity were not modified by LPS treatment in deciduas. However, FAAH protein levels and activity were diminished in PBMC after LPS treatment (p < 0.05). To analyze if the CB1 receptor is involved in LPS-induced preterm birth, we used a CB1-KO mice. We injected two different doses of LPS (10 ug/mice and 20 ug/mice of weight) and we observed that CB1-KO mice presented a lower preterm birth rate than WT mice. In summary, these data suggest that endocannabinoids are involved in pro-inflammatory response associated with LPS-induced preterm birth and that CB1 receptor is implicated in the triggering of preterm birth.