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Studies show that many of these functional impairments are associated with the hippocampus, a structure exhibiting exquisite vulnerability to developmental alcohol exposure and critically implicated in learning and memory; however, mechanisms underlying alcohol\u2010induced hippocampal deficits remain poorly understood. By utilizing a high\u2010throughput RNA\u2010sequencing (RNA\u2010seq) approach to address the neurobiological and molecular basis of prenatal alcohol\u2010induced hippocampal functional deficits, we hypothesized that chronic binge prenatal alcohol exposure alters gene expression and global molecular pathways in the fetal hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Timed\u2010pregnant Sprague\u2013Dawley rats were randomly assigned to a pair\u2010fed control (PF) or binge alcohol (ALC) treatment group on gestational day (GD) 4. ALC dams acclimatized from GDs 5\u201310 with a daily treatment of 4.5\u00a0g\/kg alcohol and subsequently received 6\u00a0g\/kg on GDs 11\u201320. PF dams received a once daily maltose dextrin gavage on GDs 5\u201320, isocalorically matching ALC counterparts. On GD 21, bilateral hippocampi were dissected, flash frozen, and stored at \u221280<jats:sup>\u00b0<\/jats:sup>C. Total RNA was then isolated from homogenized tissues. Samples were normalized to ~4nM and pooled equally. Sequencing was performed by Illumina NextSeq 500 on a 75 cycle, single\u2010end sequencing run.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA\u2010seq identified 13,388 genes, of these, 76 genes showed a significant difference (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05, log2 fold change\u00a0\u22652) in expression between the PF and ALC groups. Forty\u2010nine genes showed sex\u2010dependent dysregulation; IPA analysis showed among female offspring, dysregulated pathways included proline and citrulline biosynthesis, whereas in males, xenobiotic metabolism signaling and alaninine biosynthesis etc. were altered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that chronic binge alcohol exposure during pregnancy dysregulates fetal hippocampal gene expression in a sex\u2010specific manner. Identification of subtle, transcriptome\u2010level dysregulation in hippocampal molecular pathways offers potential mechanistic insights underlying FASD pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1334","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T12:24:59Z","timestamp":1559132699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hippocampal transcriptome reveals novel targets of FASD pathogenesis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-9991","authenticated-orcid":false,"given":"Raine","family":"Lunde\u2010Young","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josue","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Orzabal","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kranti","family":"Konganti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hillhouse","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Threadgill","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9778-5224","authenticated-orcid":false,"given":"Jayanth","family":"Ramadoss","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"issue":"5","key":"e_1_2_8_2_1","first-page":"4068","article-title":"A possible anti\u2010inflammatory effect of proline in the brain cortex and cerebellum of rats","volume":"55","author":"Andrade V. 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