Inflammatory agents involved in septic miscarriage.
Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormalities has improved, there is a dearth of knowledge of the causes of loss in euploid conceptuses. Maternal infections are a cause of abort in humans, but the mechanisms are not clear, so we have developed a murine model to study the mechanism of septic abortion by inducing embryonic resorption (ER) with lipopolysaccharide (LPS). We demonstrated that augmented production of nitric oxide (NO) and prostaglandins (PG) is involved in ER, and that inhibitors of their synthesis could prevent ER. Also, we observed an increase in the oxidative damage, evidenced by nitration of tyrosine proteins, due to the peroxynitrite anion. Since an association between chronic marijuana smoking and early miscarriage has been shown in women, we studied the participation of anandamide (AEA), the principal endocannabinoid, on the mechanism of action of LPS. We showed that LPS-induced NO synthesis and tissue damage were mediated by AEA, and that this endotoxin inhibited AEA degradation and increased its synthesis. These results suggest that several inflammatory molecules participate in the mechanism of early pregnancy loss and that their modulation could be useful tools to prevent it.
Laboratory of Physiopathology of Pregnancy and Labor--Center for Pharmacological and Botanical Studies (CEFYBO, CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Julieta
J
Aisemberg
Claudia
C
Vercelli
Manuel
M
Wolfson
Ana Inés
AI
Salazar
Claudia
C
Osycka-Salut
Silvia
S
Billi
María Laura
ML
Ribeiro
Mariana
M
Farina
Ana María
AM
Franchi
D000031:Abortion, Septic / Q000276:immunology / Q000503:physiopathology*; D000022:Abortion, Spontaneous / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D018836:Inflammation Mediators; D009573:Nitrites; D011453:Prostaglandins; D009569:Nitric Oxide