PMID- 33714876 OWN - NLM STAT- MEDLINE DCOM- 20210603 LR - 20210603 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 276 DP - 2021 Aug TI - Maternal exposure to a human based mixture of persistent organic pollutants (POPs) affect gene expression related to brain function in mice offspring hippocampus. PG - 130123 LID - S0045-6535(21)00592-0 [pii] LID - 10.1016/j.chemosphere.2021.130123 [doi] AB - Male and female mice pups were exposed to a low and high dose of a human relevant mixture of persistent organic pollutants (POPs) during pregnancy and lactation. Most compounds detected in the dams were found in offspring brains. The mice offspring exhibited changed expression of hippocampal genes involved in cognitive function (Adora2a, Auts2, Crlf1, Chrnb2, Gdnf, Gnal, Kcnh3), neuroinflammation (Cd47, Il1a), circadian rhythm (Per1, Clock), redox signalling (Hmox2) and aryl hydrocarbon receptor activation (Cyp1b1). A few genes were differentially expressed in males versus females. Mostly, similar patterns of gene expression changes were observed between the low and high dose groups. Effects on learning and memory function measured in the Barnes maze (not moving, escape latency) were found in the high dose group when combined with moderate stress exposure (air flow from a fan). Mediation analysis indicated adaptation to the effects of exposure since gene expression compensated for learning disabilities (escape latency, walking distance and time spent not moving in the maze). Additionally, random forest analysis indicated that Kcnh3, Gnal, and Crlf1 were the most important genes for escape latency, while Hip1, Gnal and the low exposure level were the most important explanatory factors for passive behaviour (not moving). Altogether, this study showed transfer of POPs to the offspring brains after maternal exposure, modulating the expression level of genes involved in brain function. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Myhre, Oddvar AU - Myhre O AD - Section of Toxicology and Risk Assessment, Norwegian Institute of Public Health, P. O. Box 222 Skoyen, N-0213, Oslo, Norway. Electronic address: oddvar.myhre@fhi.no. FAU - Zimmer, Karin E AU - Zimmer KE AD - Department of Preclinical Sciences and Pathology, Physiology Unit, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: karin.zimmer@nmbu.no. FAU - Hudecova, Alexandra M AU - Hudecova AM AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: alh@nilu.no. FAU - Hansen, Kristine E A AU - Hansen KEA AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: kristine.hansen@nmbu.no. FAU - Khezri, Abdolrahman AU - Khezri A AD - Department of Preclinical Sciences and Pathology, Physiology Unit, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: Abdolrahman.khezri@inn.no. FAU - Berntsen, Hanne F AU - Berntsen HF AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway; National Institute of Occupational Health, P.O. Box 8149 Dep, N-0033, Oslo, Norway. Electronic address: hanne.friis.berntsen@nmbu.no. FAU - Berg, Vidar AU - Berg V AD - Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: vidar.berg@nmbu.no. FAU - Lyche, Jan L AU - Lyche JL AD - Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: jan.l.lyche@nmbu.no. FAU - Mandal, Siddhartha AU - Mandal S AD - Centre for Chronic Disease Control, New Delhi, 110016, India. Electronic address: sid.mandal.85@gmail.com. FAU - Duale, Nur AU - Duale N AD - Section of Molecular Toxicology, Norwegian Institute of Public Health, P. O. Box 222 Skoyen, N-0213, Oslo, Norway. Electronic address: nur.duale@fhi.no. FAU - Ropstad, Erik AU - Ropstad E AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 As, Norway. Electronic address: erik.ropstad@nmbu.no. LA - eng PT - Journal Article DEP - 20210303 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 SB - IM MH - Animals MH - Brain MH - Female MH - Gene Expression MH - Hippocampus MH - Humans MH - Male MH - *Maternal Exposure MH - Maze Learning MH - Mice MH - Persistent Organic Pollutants MH - Pregnancy MH - *Prenatal Exposure Delayed Effects/genetics OTO - NOTNLM OT - Gene expression OT - Hippocampus OT - Human relevant mixtures OT - Learning and memory OT - Neurodevelopment OT - Persistent organic pollutants EDAT- 2021/03/15 06:00 MHDA- 2021/06/04 06:00 CRDT- 2021/03/14 20:49 PHST- 2020/11/10 00:00 [received] PHST- 2021/01/19 00:00 [revised] PHST- 2021/02/22 00:00 [accepted] PHST- 2021/03/15 06:00 [pubmed] PHST- 2021/06/04 06:00 [medline] PHST- 2021/03/14 20:49 [entrez] AID - S0045-6535(21)00592-0 [pii] AID - 10.1016/j.chemosphere.2021.130123 [doi] PST - ppublish SO - Chemosphere. 2021 Aug;276:130123. doi: 10.1016/j.chemosphere.2021.130123. Epub 2021 Mar 3.