Placental toxicity of cadmium in the rat: an ultrastructural study.

Pregnant rats on day 18 of gestation were injected s.c. with 40 mumol/kg CdCl2 which caused fetal death and placental necrosis. The placental changes were studied by electron microscopy and indicate that there is a direct placental toxic effect of cadmium which appears targeted at the trophoblast and, in particular, trophoblast cell layer II. Findings in cell layer II which suggest a toxic effect were lysosomal vesiculation, 'buckshot' nuclear chromatin clumping, nucleolar changes and apparent mitochondrial calcification. Furthermore, the selectivity of the effect on cell layer II and the rapidity of the necrosis are also consistent with a toxic effect. Trophoblast cell layer II first undergoes necrosis, but is rapidly followed by the rest of the trophoblast. Many of the changes at this necrotic stage suggest a secondary ischaemic effect or a combined ischaemic and toxic effect. Therefore it appears that cadmium induces placental necrosis via a direct effect on the trophoblast, especially on layer II.