PMID- 30836164 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20200408 IS - 1879-3185 (Electronic) IS - 0300-483X (Linking) VI - 418 DP - 2019 Apr 15 TI - Maternal exposure to low dose BDE209 and Pb mixture induced neurobehavioral anomalies in C57BL/6 male offspring. PG - 70-80 LID - S0300-483X(18)30228-2 [pii] LID - 10.1016/j.tox.2019.02.016 [doi] AB - Polybrominated diphenyl ethers (PBDEs) and lead (Pb) are common pollutants that co-exist in the environment. These chemicals may be associated with autism spectrum disorder (ASD), yet direct evidence is lacking. More importantly, how co-exposure of these chemicals might affect ASD has never been explored. For assessing the relationship between PBDE/Pb exposure and ASD, pregnant C57BL/6 J female mice were exposed to BDE209 (0.12 ng/day), Pb (1.2 ng/day), or a BDE209/Pb mixture from gestational day (GD) 9.5 to postnatal day (PND) 21 using ALZET osmotic pumps. Polyinosinic-polycytidylic acid (poly I:C) was included as a positive control, as its single dose injection (20 mg/kg.bw; i.p.) at mid-pregnancy (GD 12.5) produces ASD-like behaviors in mouse offspring. These ASD-like phenotypes include decreased preference for social novelty, increased marble burying behavior, and learning impairment. Similar to the poly I:C control, perinatal exposure to Pb or BDE209/Pb mixture elicited increased marble burying and learning impairment, but it had no effect on sociability. Consistent with these behavioral anomalies, Pb and BDE209/Pb co-exposure as well as poly I:C exposure increased the production of pro-inflammation cytokines interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), and interleukin 17 A (IL-17 A) in the serum, and decreased neuronal cells in the CA1 and CA3 subregions of the hippocampus. The majority of these changes in the BDE209/Pb mixture group were due to the effect of Pb rather than BDE209. However, BDE209/Pb co-exposure elicited a synergistic increase in the production of IL-4, IL-6, TNFalpha, IFNgamma, and IL-17A in the serum. BDE209 exposure alone also significantly affected spatial learning and increased the production of IL-10, TNFalpha, and IL-17 A in the serum of male offspring. Our work demonstrates that perinatal exposure to a low dose of Pb or the BDE209/Pb mixture, although it did not induce typical ASD-like symptoms, elicited restricted, repetitive patterns of behavior and affected learning in male offspring. In addition, the synergistic increase in the systemic inflammatory response in the BDE209/Pb co-exposure group underscores the importance of evaluating chemical mixtures in disease onset. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Chen, Yuanhong AU - Chen Y AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325035, PR China; Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Liu, Shuyun AU - Liu S AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Xu, Hui AU - Xu H AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Zheng, Huiying AU - Zheng H AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Bai, Chenglian AU - Bai C AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Pan, Wenhao AU - Pan W AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Zhou, Huanhuan AU - Zhou H AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. FAU - Liao, Min AU - Liao M AD - School of Basic Medicine, Wenzhou Medical University, Wenzhou 325035,PR China. FAU - Huang, Changjiang AU - Huang C AD - Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. Electronic address: cjhuang5711@163.com. FAU - Dong, Qiaoxiang AU - Dong Q AD - The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325035, PR China; Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, PR China. Electronic address: dqxdong@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190302 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Cytokines) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Inflammation Mediators) RN - 2P299V784P (Lead) RN - 4IL61GN3YI (lead chloride) RN - N80BQ29A0H (decabromobiphenyl ether) SB - IM MH - Animals MH - Autism Spectrum Disorder/blood/*chemically induced/physiopathology/psychology MH - Behavior, Animal/*drug effects MH - Cell Death/drug effects MH - Cytokines/blood MH - Female MH - Gestational Age MH - Grooming/drug effects MH - Halogenated Diphenyl Ethers/*toxicity MH - Hippocampus/*drug effects/metabolism/pathology/physiopathology MH - Inflammation Mediators/blood MH - Lead/*toxicity MH - Male MH - Maternal Exposure/adverse effects MH - Maze Learning/drug effects MH - Mice, Inbred C57BL MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Stereotyped Behavior/drug effects OTO - NOTNLM OT - Autism spectrum disorder OT - BDE209 OT - Behavioral assessment OT - Environmental pollutants OT - Lead EDAT- 2019/03/06 06:00 MHDA- 2020/04/09 06:00 CRDT- 2019/03/06 06:00 PHST- 2018/08/08 00:00 [received] PHST- 2019/01/26 00:00 [revised] PHST- 2019/02/28 00:00 [accepted] PHST- 2019/03/06 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/03/06 06:00 [entrez] AID - S0300-483X(18)30228-2 [pii] AID - 10.1016/j.tox.2019.02.016 [doi] PST - ppublish SO - Toxicology. 2019 Apr 15;418:70-80. doi: 10.1016/j.tox.2019.02.016. Epub 2019 Mar 2.