title: In Utero Exposure to Diethylhexyl Phthalate Affects Rat Brain Development: A Behavioral and Genomic Approach.
abstract: Diethylhexyl phthalate (DEHP) is one of the most widely utilized phthalate plasticizers. Previous studies have demonstrated that gestational or postnatal DEHP exposure induced adverse effects on rat brain development and function. In this study, we investigated the effects of gestational DEHP exposure on gene expression profiling in neonatal rat brain and cognitive function change at adulthood. Adult Sprague Dawley dams were orally treated with 10 or 750 mg/kg DEHP from gestational day 12 to 21. Some male pups were euthanized at postnatal day 1 for gene expression profiling, and the rest males were retained for water maze testing on postnatal day (PND) 56. DEHP showed dose-dependent impairment of learning and spatial memory from PND 56 to 63. Genome-wide microarray analysis showed that 10 and 750 mg/kg DEHP altered the gene expression in the neonatal rat brain. Ccnd1 and Cdc2, two critical genes for neuron proliferation, were significantly down-regulated by DEHP. Interestingly, 750 mg/kg DEHP significantly increased Pmch level. Our study demonstrated the changed gene expression patterns after in utero DEHP exposure might partially contribute to the deficit of cognitive function at adulthood.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. linhanwenzhou@wzhealth.com.
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. yuankaiming@aliyun.com.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. gerenshan2@163.com.
authors.forename: Linyan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. shiwenliu77@gmail.com.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. shiwenliu77@gmail.com.
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. hgx@wzmc.edu.cn.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. lianqingquanmz@163.com.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. r_ge@yahoo.com.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D023281:Genomics; D008297:Male; D018782:Maze Learning; D010795:Phthalic Acids; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; C032279:phthalic acid; D004051:Diethylhexyl Phthalate
keywords: DEHP; brain development; cognitive function; proliferation; rat