[[Studies on cadmium toxicity in early development of mouse ova. ]]

The purpose of the present experiments was to examine the effect of cadmium on mouse germ cells when this substance was given subcutaneously to the animal in the second meiotic metaphase. Furthermore, its mechanism of action was investigated on the basis of in vitro cultivation, enzymic histochemistry and residue analysis. The progress of gestation after implantation was also followed up. The results obtained were as follows. 1) When cadmium was administered to mice at dose levels of 0.075, 0.15, 0.3, 0.6, 1.2 and 2.4 mg/kg, the fertilization rate (2-cell cleavage rate) was found to be normal at 36 hours after ovulation, but the ratio of normal ova decreased at 84 hours in proportion to increase in the cadmium dose. 2) The ratio of normal ova was 59.9, 39.7 and 11.1% at 38, 62 and 86 hours after ovulation These findings indicate that, during the process of oval growth from the 2-cell to blastocyst stage, degeneration of the ova was gradually induced. 3) To study the developmental ability of the ova as affected by cadmium, 2-cell ova obtained from cadmium-treated mice were cultured in a chemically defined medium. As a result, about 87.0% of the ova ceased to grow by the end of 48 hours of cultivation. 4) Two-cell ova obtained from mice with no cadmium treatment were cultured in a medium containing cadmium. It was found that oval growth was hampered at 4 ppm and over of the substance, but not at 2 ppm. 5) Following administration of 5 mg/kg cadmium, its content in the uterus and ovary was determined. The mean cadmium content was 1.58 +/- 0.7 ppm for the former and 2.42 +/- 1.4 ppm for the latter. In view of the above findings, it was clear that the oval fragility did not result from cadmium in the environment where the embryos grew up. 6) Following administration of 0.15 mg/kg cadmium, all mice were sacrificed on day 18 of gestation to examine the progress of gestation. As a result, the ratio of post- and pre-implantation loss was significantly high as compared to the control. 7) One-cell and 2-cell ova from cadmium-treated mice were examined by means of enzymic histochemistry. Although no abnormality was demonstrated in the 1-cell ova, SDH and NADH2-DH were markedly reduced in the 2-cell ova. NADH2-DH, in particular, decreased quickly from 38 post-ovulative hours onwards.