Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate
Hannas, BR; Lambright, CS; Furr, J; Howdeshell, KL; Wilson, VS; Gray, LE
HERO ID
788239
Reference Type
Journal Article
Year
2011
Language
English
PMID
| HERO ID | 788239 |
|---|---|
| In Press | No |
| Year | 2011 |
| Title | Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate |
| Authors | Hannas, BR; Lambright, CS; Furr, J; Howdeshell, KL; Wilson, VS; Gray, LE |
| Journal | Toxicological Sciences |
| Volume | 123 |
| Issue | 1 |
| Page Numbers | 206-216 |
| Abstract | Several phthalate esters have been linked to the Phthalate Syndrome, affecting male reproductive development when administered to pregnant rats during in utero sexual differentiation. The goal of the current study was to enhance understanding of this class of compounds in the Sprague Dawley (SD) fetal rat following exposure on gestational days (GDs) 14-18 by determining the relative potency factors for several phthalates on fetal testes endpoints, the effects of a nine phthalate mixture on fetal testosterone (T) production, and differences in SD and Wistar (W) strain responses of fetal T production and testicular gene expression to di(2-ethylhexyl) phthalate (DEHP). We determined that diisobutyl phthalate (DIBP) and diisoheptyl phthalate (DIHP) reduced fetal testicular T production with similar potency to DEHP, whereas diisononyl phthalate (DINP) was 2.3-fold less potent. DINP was also less potent at reducing StAR and Cyp11a gene expression levels, whereas DIBP was slightly more potent than DEHP. We observed that administration of dilutions of a mixture of nine phthalates (DEHP, DIHP, DIBP, dibutyl-, benzyl butyl-, dicyclohexyl-, diheptyl-, dihexyl-, and dipentyl phthalate) reduced fetal T production in a dose-dependent manner best predicted by dose addition. Finally, we found that the differential effects of in utero DEHP treatment on epididymal and gubernacular differentiation in male SD and W rats (0, 100, 300, 500, 625, 750, or 875 mg DEHP/kg/day) are likely due to tissue-specific strain differences in the androgen and insl3 signaling pathways rather than differential effects of DEHP on fetal testis T and insl3 production. |
| Doi | 10.1093/toxsci/kfr146 |
| Pmid | 21633115 |
| Wosid | WOS:000294557500019 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | endocrine disruptors; endocrine toxicology; testis; endocrine toxicology; reproductive and developmental toxicology; developmental toxicity; prenatal; reproductive and developmental toxicology |
| Is Peer Review | Yes |
| Relationship(s) |
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