Non-monotonic dose effects of in utero exposure to di(2-ethylhexyl) phthalate (DEHP) on testicular and serum testosterone and anogenital distance in male mouse fetuses

被引:108
作者
Rylee Phuong Do [1 ]
Stahlhut, Richard W. [2 ]
Ponzi, Davide [1 ]
vom Saal, Frederick S. [1 ]
Taylor, Julia A. [1 ]
机构
[1] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA
[2] Univ Rochester, Dept Obstet & Gynecol, Med Ctr, Rochester, NY 14642 USA
关键词
Phthalates; DEHP; MEHP; Testosterone; Anogenital distance; Non-monotonic dose-response; ENDOCRINE-DISRUPTING CHEMICALS; DI-(2-ETHYLHEXYL) PHTHALATE; REPRODUCTIVE DEVELOPMENT; DIETHYLHEXYL PHTHALATE; LACTATIONAL EXPOSURE; DYSGENESIS SYNDROME; SEXUAL-DIFFERENTIATION; MALE INFANTS; HEALTH; MECHANISMS;
D O I
10.1016/j.reprotox.2012.09.006
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. Epidemiological studies suggest that DEHP decreases masculinization of male fetuses. Numerous rat studies report DEHP reduces fetal testosterone production at doses greatly exceeding human exposure. We fed pregnant CD-1 mice 0.5-500,000 mu g/kg/day DEHP from gestation day (CD) 9-18 and examined mothers and male fetuses on GD 18. We assessed non-monotonic dose-response by adding a quadratic term to a simple linear regression model. Except at the 500,000 mu g/kg/day dose, DEHP stimulated an increase in maternal and fetal serum testosterone and increased anogenital distance (AGD). Non-monotonic dose-response curves were noted for AGD and maternal, and testis testosterone (P values 0.013-0.021). Because data from our highest dose (500,000 mu g/kg/day) did not differ significantly from controls, this dose could have been incorrectly assumed to be the NOAEL had we only tested very high doses, as is typical in studies for regulatory agencies. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:614 / 621
页数:8
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