Inhibition of sterologenesis in brain and liver of fetal and suckling rats from dams fed di-2-ethylhexyl phthalate plasticizer

The effect of di-2-ethylhexyl phthalate (DEHP) on lipid metabolism was studied in liver and brain from fetal rats taken 3 days before parturition from dams receiving dietary DEHP during gestation. In fetuses from rats receiving 0.5% or 1.0% DEHP in a stock diet, the incorporation of¹⁴C-acetate and labeled mevalonate (³H or¹⁴C) into the C₂₇ sterols, C₃₀ sterols, and squalene fractions of brain tissue incubated in vitro was significantly reduced between the confidence limits P<0.05 to P<0.001. When liver from fetuses was incubated with labeled mevalonate, incorporation of label into the C₂₇ sterol and C₃₀ sterol fractions was significantly reduced as well (P<0.02 to P<0.001), whereas incorporation of labeled mevalonate into the squalene fraction was not significantly altered. The incorporation of¹⁴C-acetate into total hepatic lipids of the fetal rats was also studied, and statistically significant reductions in incorporation were observed in the lanosterol fraction (P<0.001), the combined fraction of sterol esters + squalene (P<0.02), and the combined fraction of cholesterol + diglycerides (P<0.01). No significant changes were observed in the incorporation of¹⁴C-acetate into phospholipids, free fatty acids, or triglycerides. In 8-day old suckling rats delivered from dams fed 0.5% DEHP for the last 16 days of gestation and maintained on the same diet during the nursing period, the incorporation of¹⁴C-mevalonate into hepatic C₂₇ sterols, in vitro, was significantly depressed (P<0.05) whereas in corporation into C₃₀ sterols and squalene was similar to control values. In these same suckling rats, body weights were significantly lower in the control group (21.7 vs. 18.8 g, P<0.01), whereas liver weight as a % of body weight was significantly higher (P<0.01) in rats nursing from the DEHP-fed dams. The results indicate that the inhibitory effect of dietary DEHP on lipid metabolism in the mature rat is transmitted across the placental barrier to the developing fetus and that the abnormal pattern of lipid metabolism in rats delivered from DEHP-fed females is only partially restored to normal during the suckling periods.