Nicotine protects fetus against LPS-induced fetal growth restriction through ameliorating placental inflammation and vascular development in late pregnancy in rats.

Abstract

Our previous work has shown that nicotine suppressed lipopolysaccharide (LPS)-induced placental inflammation by inhibiting cytokine release as well as infiltration of leukocytes into the placenta through the cholinergic anti-inflammatory pathway. Nicotine also increased fetal survival and restored pup weight. In the present study, we aim to further investigate if fetal growth restriction (FGR) occurs with LPS treatment, and evaluate the protective effects of nicotine on fetuses in late gestation of rats. Pregnant Sprague-Dawley rats were divided into control group, nicotine group, LPS group and LPS + nicotine group. Rats were first pretreated with nicotine or vehicle by subcutaneous injection on gestation day (GD)14 and GD15, followed by LPS or vehicle intraperitoneal injection on GD16, and were killed on GD18. Loss of fetuses, number and weights of live fetuses and weights of placentas were recorded. Placentas were collected to evaluate placental pathology and determine inflammatory cytokines and vascular endothelial growth factor (VEGF) levels. We found that LPS treatment increased levels of placental inflammatory cytokines and placental pathological damage, decreased levels of VEGF, reduced number of live fetuses and induced FGR. Pretreatment with nicotine reversed LPS-induced high levels of placental inflammatory cytokines, low levels of placental VEGF and placental pathological damage, then rescued the number and weights of live fetuses. These data demonstrated that activation of the cholinergic anti-inflammatory pathway by nicotine protected fetus against LPS-induced FGR through ameliorating placental inflammation and vascular development in late pregnancy in rats. It may be an alternative therapeutic strategy for inflammation- induced FGR in late pregnancy.

• Authors: Junjie Bao, Yong Zou, Yuanyuan Liu, Li Yuan, Robert E Garfield, Huishu Liu
• Journal: Bioscience reports (Biosci Rep) Vol. 39 Issue 7 (07 31 2019) ISSN: 1573-4935 [Electronic] England
• PMID: 31209145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Author(s).

Chemical References

• Cytokines
• Lipopolysaccharides
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Nicotine

Topics

• Animals
• Blood Vessels (drug effects, growth & development)
• Cytokines (genetics)
• Female
• Fetal Growth Retardation (chemically induced, drug therapy, genetics, pathology)
• Fetus
• Gene Expression Regulation, Developmental (drug effects)
• Humans
• Inflammation (chemically induced, drug therapy, pathology)
• Lipopolysaccharides (toxicity)
• Nicotine (pharmacology)
• Placenta (drug effects, metabolism, pathology)
• Pregnancy
• Rats
• Vascular Endothelial Growth Factor A (genetics)