title: Combined Effects of Gestational Phthalate Exposure and Zinc Deficiency on Steroid Metabolism and Growth.
abstract: Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of di-2-ethylhexyl phthalate (DEHP) through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS. In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to hepatic acute-phase response and zinc accumulation. The latter could compromise zinc availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically affected maternal progesterone and aldosterone, and presented evidence of increased androgen aromatization activity in maternal and fetal tissues. Results stress the potential major impact of mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional and chronic disease states leading to zinc deficiency.
authors.affiliation: Departments of Nutrition and of Environmental Toxicology, University of California, Davis, California 95616.
authors.forename: Johnathan R
authors.initials: JR
authors.lastname: Nuttall
authors.affiliation: Departments of Nutrition and of Environmental Toxicology, University of California, Davis, California 95616.
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Kucera
authors.affiliation: Departments of Nutrition and of Environmental Toxicology, University of California, Davis, California 95616.
authors.forename: Suangsuda
authors.initials: S
authors.lastname: Supasai
authors.affiliation: Departments of Nutrition and of Environmental Toxicology, University of California, Davis, California 95616.
authors.forename: Nilesh W
authors.initials: NW
authors.lastname: Gaikwad
authors.affiliation: Departments of Nutrition and of Environmental Toxicology, University of California, Davis, California 95616.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Oteiza
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D006130:Growth Disorders / Q000196:embryology / Q000209:etiology* / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency*
chemical_list: D013256:Steroids; D004051:Diethylhexyl Phthalate; D015032:Zinc
keywords: DEHP; di-2-ethylhexyl phthalate (DEHP); inflammation; pregnancy.; steroid; zinc deficiency