PMID- 28436303 OWN - NLM STAT- MEDLINE DCOM- 20180727 LR - 20180801 IS - 1933-7205 (Electronic) IS - 1933-7191 (Linking) VI - 25 IP - 1 DP - 2018 Jan TI - Choline Supplementation During Pregnancy Protects Against Gestational Lipopolysaccharide-Induced Inflammatory Responses. PG - 74-85 LID - 10.1177/1933719117702247 [doi] AB - OBJECTIVES: To estimate the effects and mechanisms of choline, an essential nutrient and a selective alpha7 nicotinic acetylcholine receptor (alpha7nAChR) 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 mug 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 alpha7nAChR and components of the alpha7nAChR-CAP, including nuclear factor-kappaB (NF-kappaB) and protein kinase B (AKT). Immunohistochemistry was used to localize placental sites for the p65 subunit of NF-kappaB. 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 alpha7nAChR, lowered the activation of NF-kappaB 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 alpha7nAChR and CAP. These observations have important implications for the prevention and treatment of inflammatory responses associated with pregnancy. FAU - Zhang, Min AU - Zhang M AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Han, Xinjia AU - Han X AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Bao, Juejie AU - Bao J AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Yang, Jinying AU - Yang J AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Shi, Shao-Qing AU - Shi SQ AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Garfield, Robert E AU - Garfield RE AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Liu, Huishu AU - Liu H AD - 1 Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170423 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Protective Agents) RN - N91BDP6H0X (Choline) SB - IM MH - Animals MH - Choline/administration & dosage/*therapeutic use MH - Cytokines/metabolism MH - *Dietary Supplements MH - Female MH - Inflammation/chemically induced/*drug therapy/metabolism MH - Lipopolysaccharides MH - Placenta/metabolism MH - Pregnancy MH - Protective Agents/administration & dosage/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - choline OT - cholinergic anti-inflammatory pathway OT - cytokines OT - inflammation OT - preeclampsia OT - pregnancy OT - preterm birth OT - alpha7nAChR EDAT- 2017/04/25 06:00 MHDA- 2018/07/28 06:00 CRDT- 2017/04/25 06:00 PHST- 2017/04/25 06:00 [pubmed] PHST- 2018/07/28 06:00 [medline] PHST- 2017/04/25 06:00 [entrez] AID - 10.1177/1933719117702247 [doi] PST - ppublish SO - Reprod Sci. 2018 Jan;25(1):74-85. doi: 10.1177/1933719117702247. Epub 2017 Apr 23.