Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS-Induced Embryo Resorption Model.

BACKGROUND AND PURPOSE:

Maternal infections with Gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue play an important role on the establishment of a local inflammatory process that result in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss. Here we sought to investigate whether the infiltrating PBMC modulates the decidual endocannabinoid tone and the molecular mechanisms involved.

EXPERIMENTAL APPROACH:

PBMC isolated from 7-days pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-days pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measure by radioconvertion, total decidual protein nitration by western blot (WB) and decidual FAAH nitration by immuneprecipitation followed by WB.

KEY RESULTS:

We found that co-culture of PBMC obtained from LPS-treated mice increased the level of nitration of decidual FAAH, which resulted in a negative modulation of decidual FAAH activity. Interestingly, co-treatment with progesterone or aminoguanidine prevented this effect.

CONCLUSIONS & IMPLICATIONS:

We found that LPS-treated PBMC release high amounts of nitric oxide (NO) which causes tyrosine nitration of decidual FAAH, diminishing its enzymatic activity. Inactivation of FAAH, the main degrading enzyme of anandamide and similar endocannabinoids, could lead to an increased decidual endocannabinoid tone with embryotoxic effects. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.