Choline Supplementation During Pregnancy Protects Against Gestational Lipopolysaccharide-Induced Inflammatory Responses

Objectives: To estimate the effects and mechanisms of choline, an essential nutrient and a selective 7 nicotinic acetylcholine receptor (7nAChR) agonist, on the prevention of symptoms and the effects on the cholinergic anti-inflammatory pathways (CAP) in a lipopolysaccharide (LPS)-induced inflammatory response in a rat model. Methods: Inflammation was induced by LPS treatment (1.0 g LPS/kg body weight) on gestational day (GD) 14. Nonpregnant and pregnant Sprague Dawley rats were placed on a normal choline diet (1.1 g/kg) or supplemented choline diet (5.0 g/kg) from GDs 1 to 20. Systolic blood pressure (SBP), urinary albumin, and pregnancy outcomes were recorded. On GD 20, serum and placentas were assayed for cytokines. Western blots were used to determine the expression of placenta 7nAChR and components of the 7nAChR-CAP, including nuclear factor-B (NF-B) and protein kinase B (AKT). Immunohistochemistry was used to localize placental sites for the p65 subunit of NF-B. Results: Lipopolysaccharide significantly increased SBP and urinary albumin and decreased pregnancy outcomes, and these effects were partially reversed by higher choline treatment. Choline supplementation also significantly attenuated the LPS-induced increase in serum and placental inflammatory cytokines, decreased the expression of placental 7nAChR, lowered the activation of NF-B signaling in placenta mononuclear cells, and inhibited placental AKT phosphorylation. Conclusion: This study confirms that LPS induces inflammatory conditions in pregnant rats and shows that choline supplementation protects against the inflammatory symptoms through its action on 7nAChR and CAP. These observations have important implications for the prevention and treatment of inflammatory responses associated with pregnancy.