Article ID Journal Published Year Pages File Type
5894308 Placenta 2016 12 Pages PDF
Abstract

•LPS changes angiogenic DBA+ uNK cell in mouse mid-pregnancy.•LPS down regulates uNK perforin and spiral arterioles alpha-actin expression.•Nimesulide prevents LPS-caused DBA+ uNK cell modifications impairing pregnancy.•COX-2 can trigger LPS-caused DBA+ uNK modifications and protect pregnancy against LPS.

IntroductionAlthough uterine Natural Killer (uNK) cells have cytoplasmic granules rich in perforin and granzymes, these cells do not degranulate in normal pregnancy. DBA lectin+ uNK cells produce angiogenic factors which stimulate remodeling of uterine arterioles to increase blood flow within the growing feto-placental unit. We sought to investigate the importance of COX-2 on mouse pregnancy inoculated with Gram-negative bacteria Lipopolysaccharide (LPS) by treating with a selective COX-2 inhibitor (nimesulide).MethodsWe have combined histochemical, immunohistochemical, stereological, morphometric, behavioral, and litter analyses to investigate mouse pregnancy inoculated with LPS with or without pre-treatment with nimesulide 30 min before LPS injections, focusing on DBA+ uNK cell response and viability of the pregnancy.ResultsLPS caused sickness behavior, an immature DBA+ uNK influx, decreased mature DBA+ uNK cell numbers, and triggered a new DBAlow uNK appearance. These effects of LPS, except the sickness behavior, were prevented by nimesulide. COX-2 inhibition also prevented the down-regulation of uNK perforin and spiral arteriole α-actin expression stimulated by LPS. While the litter size from Nimesulide + LPS-treated mothers was significantly smaller compared to those from LPS-treated group, nimesulide alone showed no effect on the offspring.DiscussionCollectively, our data indicate that COX-2 changes angiogenic DBA+ uNK cells in order to protect mouse pregnancy after LPS injection.

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