Transplacental toxicity of 3-methylsulphonyl-DDE in the developing adrenal cortex in mice

Abstract

The transplacental transfer, irreversible binding, and ultrastructural lesions in the fetal adrenal cortex were studied following single injections of the persistent DDT-metabolite 3-methylsulphonyl-DDE (MeSO 2-DDE) in pregnant C57B1 mice. Tape-section autoradiograms of fetuses on gestation days 12 to 17 revealed a high and tissue-specific accumulation of MeSO 2-DDE- 14C-derived radioactivity in the fetal adrenal gland. On gestation day 12 the adrenal radioactivity could be extracted with organic solvents, whereas on days 13 to 17 the radioactivity in the adrenal was irreversibly bound and could not be extracted from the tissue. As determined by computer-assisted image analysis of autoradiograms, the uptake of radioactivity in the fetal adrenals increased continuously with gestational age. Electron microscopy revealed mitochondrial degeneration and vacuolation in fetal adrenal cortex cells following injection of MeSO 2-DDE (25 mg/kg b.w.) to the pregnant dam. The lesions were clearly visible on days 14 to 15 but most pronounced on days 16 to 17. Administration of the cytochrome P450(11β) inhibitor metyrapone to pregnant dams (gestation day 17) reduced the mitochondrial toxicity induced by MeSO 2-DDE in the fetal adrenal cortex. In conclusion, the adrenocorticolytic DDT metabolite MeSO 2-DDE is transformed to a reactive, cytotoxic metabolite in the fetal adrenal cortex from its earliest stage of development. Hence, the activating cytochrome P450 form, previously proposed to be P450(11β), seems to be expressed during gestation days 12 to 13 in the adrenal cortex in the mouse fetus.