title: From the Cover: Teratogenic Effects of in Utero Exposure to Di-(2-Ethylhexyl)-Phthalate (DEHP) in B6:129S4 Mice.
abstract: Intrauterine exposure to phthalates is known to cause disorders of male reproductive function including androgen insufficiency, decreased fertility, and germ cell defects in rodents. In this study, we set out to investigate the effects of intrauterine exposure to di-(2-ethylhexyl)-phthalate (DEHP) on fetal development of the B6:129S4 mouse strain. Time-mated pregnant C57BL/6 dams were exposed to 0, 5, 250, or 500 mg/kg DEHP with corn oil as the vehicle via oral gavage from embryonic days (E)7 to 16. Survival and gross morphology of the pups were analyzed one day after the last treatment. Anogenital distance (AGD) and testicular cell functions were examined in male embryos to confirm the known effects of phthalate exposure. DEHP exposure significantly reduced the survival rate of fetuses in the 250 and 500 mg/kg dosage groups compared with the control and 5 mg/kg groups. Exposure to 250 and 500 mg/kg DEHP was teratogenic and induced exencephaly and limb malformations such as polydactyly in the B6:126S4 embryos. No gross malformations were observed in control or 5 mg/kg DEHP groups. In male embryos, exposure to both 5 and 250 mg/kg DEHP in utero was sufficient to induce the formation of multinucleated germ cells in the testes and widespread changes in mRNA expression of germ cell, interstitium and Sertoli cell-associated genes. These findings reveal that intrauterine DEHP exposure has a strong teratogenic, and lethal impact on the fetuses of B6:129S4 mouse strain.
authors.affiliation: Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Ungewitter
authors.affiliation: Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Emmi
authors.initials: E
authors.lastname: Rotgers
authors.affiliation: Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Tanika
authors.initials: T
authors.lastname: Bantukul
authors.affiliation: Gennetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences Research Triangle Park, NC, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Humphrey Hung-Chang
authors.initials: HH
authors.lastname: Yao
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death; D047109:Fetal Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000196:embryology
chemical_list: D013723:Teratogens; D004051:Diethylhexyl Phthalate
keywords: endocrine disruptor; phthalate; polydactyly; testis; germ cells