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DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS
Citation:
Wilson, V S., C R. Lambright, J. R. FURR, K. L. BOBSEINE, C. R. WOOD, G. A. HELD, AND L. E. GRAY, JR. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS. Presented at Society for the Study of Reproduction, Vancouver, British Columbia, Canada, August 1-4, 2004.
Description:
DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and L. Earl Gray, Jr. U.S. EPA, ORD, NHEERL, Reproductive Toxicology Division, RTP, NC.
Cryptorchidism is a fairly common human malformation, being displayed in 1-3 males per 100 at birth. Since only a small percentage of these lesions can be linked to known genetic defects, developmental exposure to man-made chemicals has been implicated in the increase in this reproductive malformation. Phthalate esters are high production volume, ubiquitous environmental chemicals some of which induce reproductive malformations in rats when administered during sexual differentiation. Recently we have shown that malformations in gubernacular ligament development induced by high doses of DEHP are associated with decreased insl3 gene expression, a gene critical for proper gubernacular ligaments formation. In the current study, DEHP (0, 100, 300, 600, or 900 mg/kg/day) was administered orally to Spague Dawley dams on gestation days (GD) 8 through 18. On GD18, fetal testes were evaluated for hormone production and changes in gene expression. Each fetal testis was incubated ex vivo in 500 l medium for 3 hours. Medium was collected for analysis of steroid hormone levels. Testis tissue was also collected on GD 18 and mRNA prepared to assess expression of several genes by real-time rt-PCR including insl3, SF-1, StAR, and enzymes in the steroid pathway. Results to date indicate that DEHP induced a dose dependent decrease in testosterone production that, when analyzed on a mean per litter basis, was statistically significant at 300, 600 and 900 mg/kg. Progesterone production was decreased significantly at 900 mg/kg. Insl3 gene expression was also decreased in a dose dependent manner. Effects on the expression of other testicular genes and on production of other steroid hormones are currently being examined. Thus far, the changes demonstrated are consistent with the malformations previously observed in male offspring after in utero exposure to similar doses of DEHP. Disclaimer: This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.