Participation of CB1 receptor in the embryonic resorption by LPS

WOLFSON ML; VERCELLI CA; AISEMBERG J; FRANCHI AM

Hamburg

Congreso; Joint International Congress of the American Society for Reproductive Immunology (ASRI) & the European Society for Reproductive Immunology (ESRI); 2012

ASRI & ESRI.

Marihuana remains the most popular recreationaldrug worldwide and it has been associated withadverse effects. Endocannabinoids are lipid mediatorsisolated from brain and peripheral tissues whichmimic several of the central and peripheral effectsinduced by THC, the main psychoactive compoundof Cannabis sativa.Anandamide (AEA), a major endocannabinoid, isan endogenous agonist of cannabinoid receptors thatbinds to both CB1 and CB2 receptors. Even thoughAEA is necessary for implantation, it has beenrelated to pregnancy loss in women when it is producedin excess or its degradation rate is decreased.We have developed a murine model of abortionand fetal loss, administrating LPS to BALB/c miceon day 7 of gestation, in this animals nitric oxide(NO) has a fundamental role in embryonic resorption(EmR).Previous studies from our laboratory indicate thatCB1 antagonist abolished in vitro LPS effect on NOproduction and tissue damage in uterus and deciduafrom animals in day 7 of pregnancy.Besides, peripheral blood mononuclear cells(PBMC) from pregnant mice showed higher activityof the enzyme that degrades AEA (fatty acid amidohydrolase, FAAH) than PBMC from non-pregnantanimals. LPS had no effects on FAAH activity inpregnant mice but when a progesterone (P) antagonist,such as RU486, was administrated prior to LPSstimulation, FAAH activity was decreased.The aim of this work was to study the participationof CB1 receptor in a murine model of EmR induced by LPS in CD1 mice. We performed a dose-response curve to LPS inCD1 mice at day 7 of pregnancy, using wild type (WT) mice and CB1 receptor knock-out (KO) animals. Mice were sacrificed on day 9 of pregnancy, uterine horns were removed and implantation sites were observed for fetal loss. The percentage of EmR rate was calculated as resorptions/(resorptions+healthy implantations) x100.We observed that WT mice treated with LPS 1 mg/g had an EmR 82.0 ± 11.9%, similar to the EmR obtained in the BALB/c model. But when we administrated the same dose to KO mice the EmR was 28.5 ± 3.0%. Interestingly, WT mice treated with LPS 0.5 mg/gr had an EmR 69.4 ± 22.0% butthe KO ones has only 3.4 ± 1.4% of EmR. Moreover, the KO mice which were treated with LPS 0.5 mg/gr were able to finish their pregnancy and the offsprings looked healthy.These results suggest that endocannabinoid system participates in the embryonic resorption induced byLPS.