title: Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats.
abstract: Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity. The male rats were orally exposed to either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses by gavage for 15 weeks. Testosterone and luteinizing hormone (LH) in serum were analyzed, and pathological examinations were performed for toxicity evaluation. Steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD), cell cycle and apoptosis-related proteins (p53, Chk1, Cdc2, CDK6, Bcl-2 and Bax) were measured for mechanisms exploration. MIXPs with long-term low-dose exposure could cause male reproductive toxicity to the rats, including the decrease of both serum and testicular testosterone, and the constructional damage of testis. These effects were related to down-regulated steroidogenic proteins, arresting cell cycle progression and promoting apoptosis in rat testicular cells. The results indicate that MIXPs with long-term low-dose exposure may pose male reproductive toxicity in human.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Gao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Run
authors.initials: R
authors.lastname: Xu
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Cao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Qian
authors.affiliation: Zibo Municipal Center for Disease Control and Prevention, Zibo 255026, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT 06520-8034, USA.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT 06520-8034, USA. Electronic address: q_xu68@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory for Supramolecular Medicinal Material and Applications, College of Life Sciences, Nanjing Normal University, Nanjing 210046, China; Jiangsu Province Key Laboratory for Molecular and Medicinal Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, China. Electronic address: yushuqin@njnu.edu.cn.
authors.forename: Shu-Qin
authors.initials: SQ
authors.lastname: Yu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D004952:Esters / Q000633:toxicity*; D006801:Humans; D007302:Insect Repellents / Q000633:toxicity; D007986:Luteinizing Hormone / Q000032:analysis*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000032:analysis*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004952:Esters; D007302:Insect Repellents; D010795:Phthalic Acids; D010968:Plasticizers; D013723:Teratogens; C024629:dimethyl phthalate; D003993:Dibutyl Phthalate; D013739:Testosterone; C010715:di-n-octyl phthalate; D007986:Luteinizing Hormone; D004051:Diethylhexyl Phthalate; C007379:diethyl phthalate; C027561:butylbenzyl phthalate
keywords: Apoptosis; Cell cycle; Long-term low-dose exposure; Phthalate esters; Reproductive toxicity; Steroidogenesis