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Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production
WILSON, V. S., C. R. LAMBRIGHT, N. Evans, J. R. FURR, H. Sampson, AND L. E. GRAY. Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production. Presented at Society of Toxicology (SOT) annual Meeting, San Francisco, CA, March 11 - 15, 2012.
In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis.
In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis. The DPB metabolite mono‐butyl phthalate (MBP) is hypothesized to produce these changes by a direct effect on the fetal testis. The current study investigated if direct in vitro exposure of the fetal testis to MBP would also reduce fetal androgen production as has been demonstrated ex vivo. Testes from gestation day (GD) 17 control male Sprague Dawley rat fetuses were incubated with either 0 (ethanol vehicle), 30, 100, 300 or 500 μM MBP in culture medium for 5 hr, then the media were collected and replaced with fresh media of the same treatments and incubation continued an additional 3 hrs. Four control dams were used and testes from each litter were represented across all treatments (minimum n=4 per treatment). Concurrently as a positive control, 4 GD17 dams received a single oral dose of either 0 (corn oil vehicle) or 750 mg DBP/kg. Five hrs after dosing (coincident with the first 5 hr in vitro incubation), testes from male offspring were removed and incubated ex vivo in untreated medium for 3 hr (coincident with the 3 hr in vitro incubation). Testosterone (T) production for the 5 hr and 3 hr in vitro and the concurrent 3 hr ex vivo incubations were measured in medium by RIA. As expected, ex vivo T production from the fetal testes was reduced by about 40% compared to controls after a single oral dose of DBP to the dam. In vitro MBP treatment, however, did not significantly alter T production at either time point. These data support that the effects of DBP on fetal androgen production may not be due to a direct effect on the T synthesis pathway and suggest that some extra‐testicular factors may be required. Future studies will evaluate direct effects of MBP on the profile of phthalate‐induced gene changes in this and other pathways. Disclaimer: This abstract does not reflect EPA policy.