Possible Mechanisms of Cadmium Fetotoxicity in Golden Hamsters and Mice: Uptake by the Embryo, Placenta and Ovary

Abstract

Summary. Pregnant golden hamsters and mice of different gestational ages were injected intravenously with 109CdCl2. The whole animal or the uterus and embryos were submitted to autoradiography. Cadmium administered on the 8th day accumulated in the primitive gut of the embryos. No cadmium was detected in the embryos after administration on or after the 9th day (hamster) and 11th day (mouse). This finding can be explained by the ability of cadmium to pass from the yolk-sac cavity into the primitive gut (where it is absorbed) before the closure of the vitelline duct but not later. This uptake by the embryo might explain the severe malformations produced by cadmium given on the 8th day as compared with the 9th day in the hamster. Cadmium is also heavily accumulated in the decidua (mainly the antimesometrial part), the yolk sac, the ectoplacental cone, and later in the chorioallantoic placenta\p=m-\possiblydisturbing the maternal-embryonic relationship and fetal nutrition. A high accumulation in the CL and the follicles and in the pituitary may also disturb reproductive function.

Foetotoxicity of Cadmium in Quackenbush Strain Mice and the Effects of the Metal on Uterine Alkaline Phosphatase During Pseudopregnancy

“…These findings are consistent with those of earlier studies which showed that susceptibility to the teratogenic effects of cadmium and other extraneous factors varies with the developmental stage at the time of exposure (Chiquoine 1965;Ferm 1971;Barr 1973;Gale and Ferm 1973;Wo1kowski 1974;Hall 1977). The rate of uptake and accumulation of cadmium in embryonic, placental, and ovarian tissues also depends on the day of pregnancy on which the metal is administered (Dencker 1975).…”

“…It is unlikely, therefore, that changes in progesterone and oestrogen production by the ovary following treatment with cadmium are responsible to any great extent for the foetal malformations observed in the present study. However, cadmium does accumulate in the ovary (Dencker 1975) and can decrease the activity (Unger and Clausen 1973) of cytochrome P-450 which is involved in steroid biosynthesis.…”

“…It is possible, therefore, that in vivo inhibition of alkaline phosphatase in uterine decidual cells by cadmium could lead to functional alterations in the decidua which may be detrimental to the developing embryo. This possibility gains credence from the work of Dencker (1975) who showed that, during early gestation in mice, intravenously injected cadmium accumulated not only in the maternal ovary and primitive gut of the developing embryo, but also in the uterine decidua and placenta where alkaline phosphatase activity is normally high (Murdoch et al 1978).…”

“…Thus, in males of several species cadmium induces deleterious effects on the vasculature of the testes and subsequently influences spermatogenesis and androgen production (Gunn and Gould 1970;Saksena et al 1977;Aoki and Hoffer 1978;Lau et al 1978;Niewenhuis and Fende 1978). In female mammals, cadmium may disturb maternal-embryonic relationships and cause placental necrosis, foetal resorption and embryonic developmental malformations (Parizek 1964;Ferm 1971;Schroeder and Mitchener 1971;Gale and Ferm 1973;Dencker 1975).…”

“…It is well known that cadmium inhibits the activity of many enzymes, and particularly those containing either essential thiol groups or a functionally active Zn2+ ion (see Dencker 1975;Aoki and Hoffer 1978). In this context, alkaline phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.1) from the pregnant mouse uterus is a zinc-containing metalloenzyme and is also inhibited in vitro by cadmium (Murdoch et al 1980).…”