Cadmium-Induced Ovarian Toxicity in Hamsters, Mice, and Rats

Cadmium-Induced Ovarian Toxicity in Hamsters, Mice, and Rats.REHM, S., AND WAALKES, M.P. (1988). Fundam Appl. Toxicol. 10,635–647. The effects of cadmium on the female genitaltract of Syrian hamsters (CnRGH), of four mouse strains (BALB/cAnNCr,DBA/2NCr, C57BL/ 6NCr, NFS/NCr), and two rat strains (F344/NCrand WF/NCr) were studied by light microscopy after a singlesc injection of cadmium chloride (CdCl₂). Experiments involvedanimals prior to and after sexual maturity, and employed CdCl₂doses ranging from 20 to 47.5 µmol/kg. Animals were examinedat intervals from 24 hr to 8 weeks following treatment. Syrianhamsters were most susceptible to CdCl₂-induced ovarian hemorrhagicnecrosis at all ages tested. Most severe ovarian lesions occurredin immature hamsters, in mature hamsters at high doses, andshortly before ovulation at all doses. The small arteries ofthe developing follicles and interstitial stroma seemed selectivelysusceptible to CdCl₂ toxicity while the corpora lutea, mesothelium,primordial oocytes, and the rete ovarii appeared resistant.Pretreatment with zinc acetate markedly reduced the extent ofovarian lesions in hamsters. Although reduced in weight by 45%,the hamster ovaries recovered morphologically within 2 monthsafter severe acute hemorrhagic necrosis. Uterine and cervicalstromal hemorrhages were seen only in immature hamsters at dosesof 30 µmol CdCl₂/kg. Of the mice, only the DBA/2NCr strainshowed significant CdCl₂-induced ovarian hemorrhages, and thesehemorrhages occurred at doses also producing lethal liver toxicity.Lesions of the uterus were rare. Rats showed dose- and age-dependenttoxicity in the ovaries, uterus, cervix, and liver. CdCl2 exposurein mature rats induced uterine lesions only in F344 rats, whileacute ovarian and hepatic toxicity was less severe in matureanimals of both strains. No lesions were noted after 7 daysin mature WF rats. In both rats and mice, no cycle dependencyof the ovarian lesions was evident.