Abstract
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.
Highlights
Cadmium (Cd) is an important industrial and environmental pollutant
It should be taken into account that Cd pollution is global; this metal has been placed 7th on the list of substances that pose a potential threat to human health due to their known or suspected toxicity [1]
Cd is used in a variety of manufactured products, for most people in the general population the primary sources of exposure are food and smoking tobacco [2, 3]
Summary
Cadmium (Cd) is an important industrial and environmental pollutant. It should be taken into account that Cd pollution is global; this metal has been placed 7th on the list of substances that pose a potential threat to human health due to their known or suspected toxicity [1]. Mining, smelting, and industrial use have resulted in the increased bioaccessibility of Cd in the environment, and anthropogenic sources are the most significant threat to human health [2]. Cd is used in a variety of manufactured products, for most people in the general population the primary sources of exposure are food and smoking tobacco [2, 3]. The European Food Safety Authority (EFSA) has estimated the average daily dietary exposure of Cd to be between 20.3 and 74.2 μg/day per 70 kg person [4]. Specific groups at risk of consuming higher dietary Cd than is recognized as safe are children and vegetarians [5]
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