PMID- 30036686 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20181202 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 296 DP - 2018 Oct 15 TI - Placental mechanism of prenatal nicotine exposure-reduced blood cholesterol levels in female fetal rats. PG - 31-38 LID - S0378-4274(18)31509-1 [pii] LID - 10.1016/j.toxlet.2018.07.022 [doi] AB - Clinical studies showed that intrauterine growth retardation (IUGR) neonatus had lower cholesterol concentrations in cord blood, which might be associated with increased risk of metabolic syndrome and cardiovascular diseases in adulthood. We previously observed lower blood cholesterol levels in prenatal nicotine exposure (PNE)-induced IUGR fetal rats, and this study aimed to elucidate the placental mechanism. Pregnant Wistar rats were subcutaneously injected with nicotine (2.0 mg/kg⋅d) on gestational day 9-20. In vivo, PNE increased levels of total cholesterol (TCH), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in maternal serum, while decreased levels of TCH and LDL-C in female fetal serum. Meanwhile, the expression of scavenger receptor class B type 1 (SR-B1), ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) were decreased, and the expression of liver X receptor (LXR) alpha and beta were also decreased in female placentas. In vitro, nicotine (0.1-10 muM) reduced the expression of LXRalpha, LXRbeta, SR-B1, ABCA1 and ABCG1 in a concentration dependent manner, which could be annulled by nAChR antagonist and LXR agonist. Taken together, nicotine could inhibit the expression of SR-B1, ABCA1 and ABCG1 via nAChR and LXR alpha/beta in female placentas, finally leading to reduced blood cholesterol levels in fetal rats. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zhang, Guohui AU - Zhang G AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430071, China. FAU - Zhou, Jin AU - Zhou J AD - Department of Pharmacology, Basic Medical School of Wuhan University, 185 Donghu Road, Wuchang District, Wuhan 430071, China. FAU - Huang, Wen AU - Huang W AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430071, China. FAU - Yu, Luting AU - Yu L AD - Department of Pharmacology, Basic Medical School of Wuhan University, 185 Donghu Road, Wuchang District, Wuhan 430071, China. FAU - Zhang, Yuanzhen AU - Zhang Y AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, 185 Donghu Road, Wuchang District, Wuhan 430071, China. Electronic address: zhangyuanzhen@vip.sina.com. FAU - Wang, Hui AU - Wang H AD - Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430071, China; Department of Pharmacology, Basic Medical School of Wuhan University, 185 Donghu Road, Wuchang District, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, 185 Donghu Road, Wuchang District, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn. LA - eng PT - Journal Article DEP - 20180720 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (ABCA1 protein, rat) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (Abcg1 protein, rat) RN - 0 (Cholinergic Antagonists) RN - 0 (Liver X Receptors) RN - 0 (Scarb1 protein, rat) RN - 0 (Scavenger Receptors, Class B) RN - 6M3C89ZY6R (Nicotine) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - ATP Binding Cassette Transporter 1/biosynthesis MH - ATP Binding Cassette Transporter, Subfamily G, Member 1/biosynthesis MH - Animals MH - Cell Line MH - Cholesterol/biosynthesis/*blood MH - Cholinergic Antagonists/pharmacology MH - Female MH - Fetal Growth Retardation/chemically induced/pathology MH - Fetus/metabolism MH - Humans MH - Liver X Receptors/agonists/biosynthesis MH - Nicotine/*pharmacology MH - Placenta/*drug effects/*metabolism MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Scavenger Receptors, Class B/biosynthesis OTO - NOTNLM OT - Cholesterol transport OT - Intrauterine growth retardation OT - Liver X receptor (LXR) OT - Nicotinic acetylcholine receptor OT - Placenta OT - Prenatal nicotine exposure EDAT- 2018/07/24 06:00 MHDA- 2018/09/05 06:00 CRDT- 2018/07/24 06:00 PHST- 2018/02/24 00:00 [received] PHST- 2018/07/09 00:00 [revised] PHST- 2018/07/19 00:00 [accepted] PHST- 2018/07/24 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2018/07/24 06:00 [entrez] AID - S0378-4274(18)31509-1 [pii] AID - 10.1016/j.toxlet.2018.07.022 [doi] PST - ppublish SO - Toxicol Lett. 2018 Oct 15;296:31-38. doi: 10.1016/j.toxlet.2018.07.022. Epub 2018 Jul 20.