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Updated: Mar 13, 2026
Isolation of Primary Human Decidual Cells from the Fetal Membranes of Term Placentae
Published on: April 30, 2018
Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS-Induced Embryo
Manuel Luis Wolfson1, Julieta Aisemberg1, Fernando Correa1
1Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies (CEFYBO), CONICET-UBA, Buenos Aires, Argentina.
Abstract:
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 plays an important role in the establishment of a local inflammatory process that results 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. PBMC isolated from 7-day pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-day pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measured by radioconvertion, total decidual protein nitration by Western blot (WB), and decidual FAAH nitration by immunoprecipitation followed by WB. 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. 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. J. Cell. Physiol. 232: 1441-1447, 2017. © 2016 Wiley Periodicals, Inc.
Insights
Maternal gram-negative bacterial infections can cause miscarriage. Lipopolysaccharide (LPS) exposure increases nitric oxide, which inactivates decidual fatty acid amide hydrolase (FAAH), elevating embryotoxic endocannabinoids.
Area of Science:
- Reproductive immunology
- Molecular endocrinology
- Pregnancy complications
Background:
- Maternal gram-negative bacterial infections are linked to miscarriage.
- Lipopolysaccharide (LPS) activates peripheral blood mononuclear cells (PBMC) in decidual tissue, causing inflammation and embryo resorption.
- Elevated endocannabinoid tone mediates LPS-induced pregnancy loss.
Purpose of the Study:
- To investigate how infiltrating PBMC modulate the decidual endocannabinoid tone.
- To elucidate the molecular mechanisms underlying LPS-induced pregnancy complications.
Main Methods:
- Co-culture of mouse PBMC with decidual tissue.
- Measurement of decidual fatty acid amide hydrolase (FAAH) activity.
- Assessment of protein nitration using Western blot and immunoprecipitation.
Main Results:
- LPS-activated PBMC increased nitration of decidual FAAH, reducing its activity.
- Nitric oxide (NO) released by LPS-treated PBMC caused tyrosine nitration of FAAH.
- Progesterone or aminoguanidine treatment prevented these effects.
- FAAH inactivation led to increased endocannabinoid tone, potentially causing embryotoxicity.
Conclusions:
- Inactivated decidual FAAH by LPS-induced NO contributes to early pregnancy loss.
- Modulating endocannabinoid tone presents a potential therapeutic strategy for preventing pregnancy complications.
