AUTHOR=Liu Yang , Liu Jin , Liu Anguo , Yin Hillary , Burd Irina , Lei Jun 

TITLE=Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.902096

DOI=10.3389/fimmu.2022.902096

ISSN=1664-3224

ABSTRACT=<p>The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition of <italic>Saa2</italic>, using si<italic>Saa2</italic>, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokines <italic>Il1β</italic>, <italic>Il6</italic>, and <italic>Tnfα</italic> were downregulated by si<italic>Saa2</italic> treatment. Maternal inhibition of <italic>Saa2</italic> did not change the expression of <italic>Saa1–4</italic> in the fetal brain. Explant inflammatory culture of placentas with si<italic>Saa2</italic> showed similar results to our <italic>in vivo</italic> experiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB.</p>