Cadmium-induced ovarian toxicity in hamsters, mice, and rats

The effects of cadmium on the female genital tract of Syrian hamsters (Cr:RGH), of four mouse strains (BALB/cAnNCr, DBA/2NCr, C57BL/6NCr, NFS/NCr), and two rat strains (F344/NCr and WF/NCr) were studied by light microscopy after a single sc injection of cadmium chloride (CdCl2). Experiments involved animals prior to and after sexual maturity, and employed CdCl2 doses ranging from 20 to 47.5 mumol/kg. Animals were examined at intervals from 24 hr to 8 weeks following treatment. Syrian hamsters were most susceptible to CdCl2-induced ovarian hemorrhagic necrosis at all ages tested. Most severe ovarian lesions occurred in immature hamsters, in mature hamsters at high doses, and shortly before ovulation at all doses. The small arteries of the developing follicles and interstitial stroma seemed selectively susceptible to CdCl2 toxicity while the corpora lutea, mesothelium, primordial oocytes, and the rete ovarii appeared resistant. Pretreatment with zinc acetate markedly reduced the extent of ovarian lesions in hamsters. Although reduced in weight by 45%, the hamster ovaries recovered morphologically within 2 months after severe acute hemorrhagic necrosis. Uterine and cervical stromal hemorrhages were seen only in immature hamsters at doses of greater than or equal to 30 mumol CdCl2/kg. Of the mice, only the DBA/2NCr strain showed significant CdCl2-induced ovarian hemorrhages, and these hemorrhages occurred at doses also producing lethal liver toxicity. Lesions of the uterus were rare. Rats showed dose- and age-dependent toxicity in the ovaries, uterus, cervix, and liver. CdCl2 exposure in mature rats induced uterine lesions only in F344 rats, while acute ovarian and hepatic toxicity was less severe in mature animals of both strains. No lesions were noted after 7 days in mature WF rats. In both rats and mice, no cycle dependency of the ovarian lesions was evident.