In Utero and Lactational Exposure to Diisopentyl Phthalate Induces Fetal Toxicity and Antiandrogenic Effects in Rats.

Autor:	Curi TZ; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil.; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Neubert da Silva G; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil.; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Passoni MT; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Lima Tolouei SE; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Meldola H; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Romano RM; Laboratory of Reproductive Toxicology, Department of Pharmacy, State University of Centro-Oeste, Guarapuava, PR 85040-080, Brazil., Grechi N; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Dalsenter PR; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil., Martino-Andrade AJ; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil.; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), Curitiba, PR 81531-980, Brazil.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2019 Oct 01; Vol. 171 (2), pp. 347-358.
DOI:	10.1093/toxsci/kfz159
Abstrakt:	A previous study has demonstrated exposure of Brazilian pregnant women to diisopentyl phthalate (DiPeP), which reduces fetal rat testosterone production in a dose-responsive manner. In this study, we examined gene expression of steroidogenic proteins in rat fetal testes and investigated the effects of in utero and lactational DiPeP exposure on male rat reproductive development and function. For the prenatal experiment, we orally exposed pregnant Wistar rats to DiPeP or di-n-butyl phthalate (reference phthalate) at 0, 125, 250, and 500 mg/kg/day from gestation day 14-18 and the fetal testis was evaluated for transcript expression of Star, Cyp11a1, Cyp17a1, Cyp19a1, Insl3, Ar, Esr1, Esr2, and Gper1 by real-time quantitative PCR (RT-qPCR). Diisopentyl phthalate lowered mRNA levels of key steroidogenic proteins, lending support to the previously reported reductions in fetal testosterone production. Diisopentyl phthalate also lowered fetal testis transcript levels of Insl3 and changed gene expression of some steroid hormones receptors. For the postnatal experiment, pregnant rats were exposed orally to vehicle (canola oil) and 4 DiPeP doses (1, 10, 100, and 300 mg/kg/day) between gestation day 10 and postnatal day 21. Diisopentyl phthalate induced a range of reproductive and antiandrogenic effects that are typical of the rat phthalate syndrome, including reduced anogenital distance at the highest dose, reduced weight of seminal vesicles at 10 mg/kg/day and above, and testicular morphological and functional changes. Signs of fetal toxicity were observed at the highest dose. Together, our results indicate that DiPeP, a compound relevant to the human exposure scenario, is one of the most active antiandrogenic phthalates. (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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