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.
Neuroimmunomodulation. 2010;17(3):150-2. doi: 10.1159/000258710. Epub 2010 Feb 4.
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.
尽管对染色体异常导致早期妊娠丢失的原因有了更多的了解，但对于正常染色体胚胎丢失的原因仍知之甚少。母体感染是导致人类流产的一个原因，但具体机制尚不清楚，因此我们建立了一个鼠模型，通过用脂多糖（LPS）诱导胚胎吸收（ER）来研究感染性流产的机制。我们证明，一氧化氮（NO）和前列腺素（PG）的产生增加与 ER 有关，其合成抑制剂可以预防 ER。此外，我们观察到由于过氧亚硝酸盐阴离子导致酪氨酸蛋白硝化，氧化损伤增加。由于已经在女性中证明了慢性吸食大麻与早期流产之间存在关联，我们研究了主要内源性大麻素——花生四烯酸乙醇胺（AEA）在 LPS 作用机制中的参与。我们表明，LPS 诱导的 NO 合成和组织损伤是由 AEA 介导的，这种内毒素抑制了 AEA 的降解并增加了其合成。这些结果表明，几种炎症分子参与了早期妊娠丢失的机制，其调节可能是预防它的有用工具。
