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Toxicol Sci

Title:		Di(2-Ethylhexyl) Phthalate Exposure During Prenatal Development Causes Adverse Transgenerational Effects on Female Fertility in Mice
Author(s):		Rattan S; Brehm E; Gao L; Flaws JA;
Address:		"Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802"
Journal Title:		Toxicol Sci
Year:		2018
Volume:		163
Issue:		2
Page Number:		420 - 429
DOI:		10.1093/toxsci/kfy042
ISSN/ISBN:		1096-0929 (Electronic) 1096-6080 (Print) 1096-0929 (Linking)
Abstract:		"Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant and endocrine disrupting chemical, but little is known about its effects on female reproduction. Thus, we tested the hypothesis that prenatal exposure to DEHP accelerates the onset of puberty, disrupts estrous cyclicity, disrupts birth outcomes, and reduces fertility in the F1, F2, and F3 generations of female mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 microg/kg/day and 500 and 750 mg/kg/day) from gestation day 10.5 until birth. F1 females were mated with untreated males to obtain the F2 generation. F2 females were mated with untreated males to produce the F3 generation. In all generations, the onset of puberty, estrous cyclicity, select birth outcomes, and fertility-related indices were evaluated. In the F1 generation, prenatal DEHP exposure (200 microg/kg/day) accelerated the onset of puberty, it (200 microg and 500 mg/kg/day) disrupted estrous cyclicity, and it (20 and 200 microg/kg/day) decreased fertility-related indices. In the F2 generation, ancestral DEHP exposure (500 mg/kg/day) accelerated the onset of puberty, it (20 and 200 microg/kg/day) disrupted estrous cyclicity, it (20 microg and 500 mg/kg/day) increased litter size, and it (500 mg/kg/day) decreased fertility-related indices. In the F3 generation, ancestral DEHP exposure (20, 200 microg, and 500 mg/kg/day) accelerated the onset of puberty, it (20 microg/kg/day) disrupted estrous cyclicity, and it (750 mg/kg/day) decreased female pup anogenital index. Collectively, these data indicate that prenatal DEHP exposure causes female reproductive problems in a multigenerational and transgenerational manner"
Keywords:		"Animals Diethylhexyl Phthalate/*toxicity Dose-Response Relationship, Drug Endocrine Disruptors/*toxicity Female Fertility/*drug effects Maternal Exposure/*adverse effects Mice, Inbred Strains Pregnancy Prenatal Exposure Delayed Effects/*chemically induced;"
Notes:		"MedlineRattan, Saniya Brehm, Emily Gao, Liying Flaws, Jodi A eng P01 ES022848/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. 2018/02/23 Toxicol Sci. 2018 Jun 1; 163(2):420-429. doi: 10.1093/toxsci/kfy042"