Lack of CB1 receptor reduces preterm birth rate in an LPS-induced murine model.

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

Congreso; IX SLIMP; 2022

Preterm birth (PTB) is the leading cause of morbi-mortality in neonates. Endocannabinoid system (ECs) is one of the several pathways implicated in physiopathology of reproduction and previous results from our lab have demonstrated its participation in PTB. The decidua is an essential tissue for preparing, establishing and maintaining pregnancy. Before the onset of labor, the decidua thins to facilitate labor in progress. However, a premature regression of the decidua is associated with preterm parturition. We have CD1-knock out mice for the cannabinoid receptor 1 (CB1-KO), so, we aimed to study the participation of CB1 receptor on late pregnancy and also in an inflammatory model of PTB. First, using CB1-KO mice, we analyzed different pregnancy parameters and observed that CB1-KO mice present higher reproductive efficiency than WT mice (79,45% WT vs. 90,2% CB1-KO p<0.05). Also, we observed that CB1-KO mice have increased fetal viability on day 15 of pregnancy in comparison with CB1-WT mice (96% WT vs. 100% CB1-KO p<0.05). No differences were observed neither pregnancy length nor litter size. We developed a murine model of PTB induced by two injections of LPS in CB1-KO mice (ip. 10ug/g of weight and 3h later 20ug/g of weigh respectively on day 15 of pregnancy). We observed that CB1-KO mice show lower PTB than WT mice (56% CB1-KO vs. 81,5% WT p<0.05). We analyzed the decidual weight after LPS treatment and found no differences between genotypes or treatments. However, when we analyzed the histology of the maternal-fetal interface, we observed that the decidua/placenta area was lower in LPS-treated mice in comparison with control, and the same pattern was observed both in CB1-WT and CB1-KO mice. Altogether, the results show that CB1-KO mice have higher reproductive efficiency and show a lower rate of PTB in an LPS-induced model, suggesting the central role of ECs in pregnancy.