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Di-isoheptyl Phthalate (DIHP) in utero exposure reduces testicular testosterone (T) production in fetal Sprague Dawley (SD) rats
Citation:
LAMBRIGHT, C. R., K. L. HOWDESHELL, J. R. FURR, L. E. GRAY, AND V. S. WILSON. Di-isoheptyl Phthalate (DIHP) in utero exposure reduces testicular testosterone (T) production in fetal Sprague Dawley (SD) rats. Presented at Triangle Consortium for Reproductive Biology, Durham, NC, February 23, 2008.
Impact/Purpose:
Presentation at TCRB
Description:
Exposure to DIHP, a commercial phthalate ester plasticizer used in flooring manufacturing, during the fetal period of sexual differentiation disrupts male reproductive development resulting in reproductive malformations and reduced androgen-dependent reproductive tissue weights in adult SD male rat offspring. The goal of this study was to further elucidate the effects of in utero DIHP exposure on the fetal testis hormone production and to determine the shape of the dose response curve by measuring fetal T production. Time-pregnant SD dams were dosed with either 0, 100, 300, 600 or 900 mg/kg/day DIHP from gestational day (GD) 14-18. On GD 18, all fetal testes were collected and incubated individually for 3 hours either unstimulated or stimulated with human chorionic gonadotropin (hCG, 100 mIU). Medium was collected and T levels measured by RIA. Exposure to DIHP caused a significant reduction in fetal T levels with unstimulated testes reduced at doses of 300 mg/kg/day and greater. The presence of hCG increased T production at each dose by approximately 2-fold, however T production in the stimulated testes was significantly reduced only at doses of 600 mg DIHP /kg/day and above. The unstimulated T production data are comparable with previous studies of diethylhexyl phthalate (DEHP) where a significant reduction in fetal T levels was observed at 300 mg DEHP/kg/day in SD fetal testes incubations. Taken together, these data demonstrate that exposure to DIHP during the critical period of sexual differentiation significantly impairs fetal testes T production with and without hCG at 600 mg/kg/day or 300 mg/kg/day, respectively.