PMID- 29321036 OWN - NLM STAT- MEDLINE DCOM- 20181015 LR - 20181113 IS - 1743-8977 (Electronic) IS - 1743-8977 (Linking) VI - 15 IP - 1 DP - 2018 Jan 10 TI - Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome. PG - 3 LID - 10.1186/s12989-017-0239-8 [doi] LID - 3 AB - BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. Pregnant dams were exposed to nano-titanium dioxide (nano-TiO(2)) aerosols (10 +/- 0.5 mg/m(3)) for 7-8 days (calculated, cumulative lung deposition = 217 +/- 1 mug) and on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. RESULTS: The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO(2) exposed progeny. The most notable alterations in major biologic systems included immune adaptation and organismal growth. Changes in normal physiology were linked with other tissues, including liver and kidneys. CONCLUSIONS: These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome. FAU - Stapleton, P A AU - Stapleton PA AD - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA. AD - Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA. FAU - Hathaway, Q A AU - Hathaway QA AD - Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Nichols, C E AU - Nichols CE AD - Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. FAU - Abukabda, A B AU - Abukabda AB AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, USA. FAU - Pinti, M V AU - Pinti MV AD - Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Shepherd, D L AU - Shepherd DL AD - Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - McBride, C R AU - McBride CR AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Department of Physiology, Pharmacology, and Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, 1 Medical Center Drive, Morgantown, WV, 26506-9229, USA. FAU - Yi, J AU - Yi J AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Department of Physiology, Pharmacology, and Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, 1 Medical Center Drive, Morgantown, WV, 26506-9229, USA. FAU - Castranova, V C AU - Castranova VC AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, USA. FAU - Hollander, J M AU - Hollander JM AD - Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Nurkiewicz, T R AU - Nurkiewicz TR AD - Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. tnurkiewicz@hsc.wvu.edu. AD - Toxicology Working Group, West Virginia University School of Medicine, Morgantown, WV, USA. tnurkiewicz@hsc.wvu.edu. AD - Department of Physiology, Pharmacology, and Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, 1 Medical Center Drive, Morgantown, WV, 26506-9229, USA. tnurkiewicz@hsc.wvu.edu. LA - eng GR - DGE-1144676/National Science Foundation/International GR - R01 HL128485/HL/NHLBI NIH HHS/United States GR - NSF-1003907/National Science Foundation/International GR - es024783/ES/NIEHS NIH HHS/United States GR - R56 HL128485/HL/NHLBI NIH HHS/United States GR - P30 ES005022/ES/NIEHS NIH HHS/United States GR - R00 ES024783/ES/NIEHS NIH HHS/United States GR - AHA-17PRE33660333/American Heart Association/International GR - R01 ES015022/ES/NIEHS NIH HHS/United States GR - ES015022/ES/NIEHS NIH HHS/United States GR - hl128485/HL/NHLBI NIH HHS/United States GR - 13PRE16850066/American Heart Association/International PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20180110 PL - England TA - Part Fibre Toxicol JT - Particle and fibre toxicology JID - 101236354 RN - 15FIX9V2JP (titanium dioxide) RN - D1JT611TNE (Titanium) SB - IM MH - Animals MH - Female MH - Fetal Development/*drug effects/genetics MH - Fetal Heart/drug effects/metabolism MH - Gene Expression Profiling MH - Gestational Age MH - Maternal Exposure/*adverse effects MH - Nanostructures/*toxicity MH - Pregnancy MH - Rats, Sprague-Dawley MH - Titanium/*toxicity MH - Transcriptome/*drug effects PMC - PMC5763571 OTO - NOTNLM OT - Epigenetics OT - Fetal OT - Inhalation OT - Maternal OT - Nanomaterial OT - Nanotechnology OT - Toxicology COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: not applicable CONSENT FOR PUBLICATION: The authors consent to publication. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/01/13 06:00 MHDA- 2018/10/16 06:00 PMCR- 2018/01/10 CRDT- 2018/01/12 06:00 PHST- 2017/10/04 00:00 [received] PHST- 2017/12/21 00:00 [accepted] PHST- 2018/01/12 06:00 [entrez] PHST- 2018/01/13 06:00 [pubmed] PHST- 2018/10/16 06:00 [medline] PHST- 2018/01/10 00:00 [pmc-release] AID - 10.1186/s12989-017-0239-8 [pii] AID - 239 [pii] AID - 10.1186/s12989-017-0239-8 [doi] PST - epublish SO - Part Fibre Toxicol. 2018 Jan 10;15(1):3. doi: 10.1186/s12989-017-0239-8.