PMID- 32360330 OWN - NLM STAT- MEDLINE DCOM- 20210223 LR - 20210602 IS - 1873-1708 (Electronic) IS - 0890-6238 (Print) IS - 0890-6238 (Linking) VI - 94 DP - 2020 Jun TI - Sex- and age-dependent effects of maternal organophosphate flame-retardant exposure on neonatal hypothalamic and hepatic gene expression. PG - 65-74 LID - S0890-6238(20)30051-4 [pii] LID - 10.1016/j.reprotox.2020.04.001 [doi] AB - After the phase-out of polybrominated diphenyl ethers, their replacement compounds, organophosphate flame retardants (OPFRs) became ubiquitous in home and work environments. OPFRs, which may act as endocrine disruptors, are detectable in human urine, breast milk, and blood samples collected from pregnant women. However, the effects of perinatal OPFR exposure on offspring homeostasis and gene expression remain largely underexplored. To address this knowledge gap, virgin female mice were mated and dosed with either a sesame oil vehicle or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day (GD) 7 to postnatal day (PND) 14. Hypothalamic and hepatic tissues were collected from one female and one male pup per litter on PND 0 and PND 14. Expression of genes involved in energy homeostasis, reproduction, glucose metabolism, and xenobiotic metabolism were analyzed using quantitative real-time PCR. In the mediobasal hypothalamus, OPFR increased Pdyn, Tac2, Esr1, and Pparg in PND 14 females. In the liver, OPFR increased Pparg and suppressed Insr, G6pc, and Fasn in PND 14 males and increased Esr1, Foxo1, Dgat2, Fasn, and Cyb2b10 in PND 14 females. We also observed striking sex differences in gene expression that were dependent on the age of the pup. Collectively, these data suggest that maternal OPFR exposure alters hypothalamic and hepatic development by influencing neonatal gene expression in a sex-dependent manner. The long-lasting consequences of these changes in expression may disrupt puberty, hormone sensitivity, and metabolism of glucose, fatty acids, and triglycerides in the maturing juvenile. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Adams, Samantha AU - Adams S AD - Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. FAU - Wiersielis, Kimberly AU - Wiersielis K AD - Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. FAU - Yasrebi, Ali AU - Yasrebi A AD - Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. FAU - Conde, Kristie AU - Conde K AD - Graduate Program in Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. FAU - Armstrong, Laura AU - Armstrong L AD - Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. FAU - Guo, Grace L AU - Guo GL AD - Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. FAU - Roepke, Troy A AU - Roepke TA AD - Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Graduate Program in Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. Electronic address: ta.roepke@rutgers.edu. LA - eng GR - T32 ES007148/ES/NIEHS NIH HHS/United States GR - R21 ES027119/ES/NIEHS NIH HHS/United States GR - R25 ES020721/ES/NIEHS NIH HHS/United States GR - P30 ES005022/ES/NIEHS NIH HHS/United States GR - R01 GM104037/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200429 PL - United States TA - Reprod Toxicol JT - Reproductive toxicology (Elmsford, N.Y.) JID - 8803591 RN - 0 (Flame Retardants) RN - 0 (Organophosphates) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Animals, Newborn MH - Female MH - Flame Retardants/*toxicity MH - Gene Expression Regulation, Developmental/*drug effects MH - Glucose/metabolism MH - Hypothalamus/*drug effects/metabolism MH - Lipid Metabolism MH - Liver/*drug effects/metabolism MH - Male MH - Maternal-Fetal Exchange MH - Mice, Inbred C57BL MH - Organophosphates/*toxicity MH - Pregnancy PMC - PMC7303001 MID - NIHMS1592365 OTO - NOTNLM OT - Endocrine disruptors OT - Gene expression OT - Hypothalamus OT - Liver OT - Maternal exposure OT - Organophosphate flame retardants OT - Sex differences COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/05/04 06:00 MHDA- 2021/02/24 06:00 PMCR- 2021/06/01 CRDT- 2020/05/04 06:00 PHST- 2019/07/31 00:00 [received] PHST- 2020/03/31 00:00 [revised] PHST- 2020/04/03 00:00 [accepted] PHST- 2020/05/04 06:00 [pubmed] PHST- 2021/02/24 06:00 [medline] PHST- 2020/05/04 06:00 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - S0890-6238(20)30051-4 [pii] AID - 10.1016/j.reprotox.2020.04.001 [doi] PST - ppublish SO - Reprod Toxicol. 2020 Jun;94:65-74. doi: 10.1016/j.reprotox.2020.04.001. Epub 2020 Apr 29.