Progesterone and Anandamide in Pregnancy Loss

WOLFSON, MANUEL; CORREA, FERNANDO; LEISHMAN, EMMA; VERCELLI, CLAUDIA; CYMERYNG, CORA; SCHANDER, JULIETA; BLANCO, JULIETA; BRADSHAW, HEATHER; FRANCHI, ANA

Mar del Plata

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta and V Latin American Symposium on Reproductive Immunology Meeting; 2015

SLIMP/LASRI

It has been shown that abortion and changes in the endocannabinoidsystem (eCS) in peripheral lymphocytes of pregnant women are closelyassociated.In a murine model of LPS-induced embryonic resorption (EmR), westudied the involvement of the eCS and infiltrating immune cells in theimplantation sites, and its possible regulation by progesterone.We observed an increase in the plasma levels anandamide (AEA), the mostabundant endocannabinoid in the uterus. On the other hand, we found thatLPS induced less EmR in cannabinoid receptor type 1 (CB1) knock-out mice,together with a lower increase in progesterone plasma levels. We demonstratedthe presence of eCS in murine peripheral blood mononuclear cells(PBMC) and a higher activity of PBMC fatty acid amide hydrolase activity(FAAH) from pregnant mice when compared to non-pregnant mice.Moreover,we observed that progesterone, via its classical receptor (PR), hada protective effect on FAAH activity. Given that 70% of PBMC are T-lymphocytes,we demonstrated the presence of PR in this subpopulation.During EmR, decidua is infiltrated with immune cells, suffers importantdamage and is finally expelled. Using a co-culture system, we investigatedthe effects of leukocyte infiltration on decidual FAAH activity. When deciduasfrom control mice were cultured in the presence of PBMC from LPStreatedanimals, decidual FAAH activity was abolished. This effect wasreversed by the co-administration of progesterone or aminoguanidine (aselective inhibitor of iNOS). When deciduas were co-cultured with PBMCfromLPS treated mice,we observed an increase in decidual protein nitration,particularly in FAAH. This effect was reversed by progesterone treatment.This work shows that eCS is involved in the LPS-induced EmR and thatchanges in the decidua are influenced both by infiltrating immune cells aswell as by alterations in the endocrine system.