You are here:
DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS INSL3 GENE EXPRESSION AND STERIOD 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 INSL3 GENE EXPRESSION AND STERIOD HORMONE SYNTHESIS. Presented at Workshop on the Environment, Reproductive Health and Fertility, Copenhagen, Denmark, January 15-18, 2005.
Description:
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 thisreproductive malformation. Phthalate estersare 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 ml 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.