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

Abstract

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 (CdCl 2). Experiments involved animals prior to and after sexual maturity, and employed CdCl 2 doses ranging from 20 to 47.5 μmol/kg. Animals were examined at intervals from 24 hr to 8 weeks following treatment. Syrian hamsters were most susceptible to CdCl 2-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 CdCl 2 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 ≥ 30 μmol CdCl 2/kg. Of the mice, only the DBA 2NCr strain showed significant CdCl 2-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. CdCl 2 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.