Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats

Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5 mg/kg b.w. on the balance of sex hormones by estimating estradiol (E₂) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17β-E₂. Additionally, the uterine weight, histopathological changes in the uterus and ovaries, the regularity of the estrous cycle, Cd bioaccumulation in uterine tissue, and selected biochemical parameters of oxidative stress were determined. A long period of observation (three and six months following the administration period) was used to assess whether the existing effects are reversible. The lowest dose of Cd caused effects similar to 17β-E₂: an increase of E₂ concentration in the uterus, endometrial epithelium thickness, and disturbed estrous cycle with estrus phase prolongation. The obtained results suggest that Cd causes nonlinear response. Higher doses of Cd caused a significant decrease in E₂ concentration in the uterus and plasma, estrous cycle disturbances, endometrium atrophy, and structural damage in the ovaries. This dose additionally induces lipid peroxidation in the uterine tissues. It is noteworthy that a prolonged time of observation after terminating the exposure showed persistent changes in the concentration of E₂ in uterine tissue, as well as alterations in estrous cycle phases, and an increase in lipid peroxidation in the uterus. Moreover, significant positive correlations between the plasma E₂ concentration and endometrial epithelium thickness in all studied groups were found. In summary, subchronic oral Cd exposure of female rats may result in impaired fertility processes.