COX-2 plays a role in angiogenic DBA⁺ uNK cell subsets activation and pregnancy protection in LPS-exposed mice

Introduction Although 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). Methods We 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. Results LPS caused sickness behavior, an immature DBA⁺ uNK influx, decreased mature DBA⁺ uNK cell numbers, and triggered a new DBA^low 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. Discussion Collectively, our data indicate that COX-2 changes angiogenic DBA⁺ uNK cells in order to protect mouse pregnancy after LPS injection.