Cadmium (Cd) is regarded as a potential endocrine disruptor. However, the exact mechanism by which this metal may interfere with the reproductive system has not yet been elucidated. The present study aimed to investigate the effect of subacute Cd oral administration at daily doses of 0.09, 1.8, and 4.5 mgCd/kg b.w. and the impact of Cd on sex hormones (estradiol (E2) and progesterone (P)) in the plasma and uterus, as well as on estrous cyclicity and histopathological changes in uterine and ovary in female rats after terminating the exposure and after a prolonged observation period (3 months). Moreover, Cd bioaccumulation in the uterine and brain tissue of rats was analyzed. The study revealed that oral Cd exposure induced changes in the plasma levels of steroid hormones: decrease in E2 and increase in P after the highest dose of Cd. Probably, for the first time, it was evidenced that circulation sex hormone disturbances in Cd-exposed rats caused irregular estrous cycle, persisting for 3 months after exposure termination; no alterations in these hormone levels in uterine tissue were noted. Cd did not induce estradiol-like hyperplasia of endometrium, but resulted in endometrial edema irrespective of the dose, and caused damage of the ovaries after the highest dose. In summary, subacute oral exposure of female rats to Cd may lead to long-term disturbances in reproductive system.

Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.

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.

The aim of this study was to investigate the cadmium (Cd), copper (Cu), zinc (Zn), iron (Fe), magnesium (Mg) and calcium (Ca) concentrations in uterine cancer and uterine myoma. Tissue levels of six elements in 15 uterine cancers and 28 uterine myomas were measured by atomic absorption spectrometry. The samples were collected from women aged 32-79 (uterine myomas, uterine cancer and non-lesion uterine tissues from the same women). The results showed that the tissue Cd concentration was significantly lower in myoma than in non-lesion tissue. In uterine cancer, however, it was statistically significant, but only slightly lower than controls (the non-lesion uterine tissue). In the investigated tissues, the correlation between Cd concentration and age was found, but no effect of menopausal status or smoking habits on Cd level was detected. In uterine cancer tissue, a significant increase in Ca concentration and an insignificant increase in Mg level was observed when compared to normal uterine tissue. In uterine myoma, a significant increase of Mg and Mg/Ca ratio, as well as a decrease in Fe concentration were found. Statistical analysis showed no correlation between smoking habits, age, menopausal status and concentration of Cu, Zn, Fe, Mg and Ca trace metals in myoma or cancer tissue.

A significantly lowered Zn/tPSA ratio appears to be a sensitive marker of neoplastic lesions, PCa and PIN, regardless of age. In men under 65 years, the Zn/IGF-1 ratio was reduced, depending on the stage of neoplastic lesions (PIN>PCa). These finding can be useful in early diagnosis of prostate cancer.

Cadmium (Cd) is one of the environmental metalloestrogens, and its role in uterine tissues has not yet been fully elucidated. The aim of the study was to investigate estrogenic properties of Cd in uterine tissues by analyzing the expression of estrogen receptor (ER) and progesterone receptor (PR) as well as estrogen and progesterone levels in serum and Cd concentrations in blood and tissues. The samples of tissues (leiomyoma and surrounding myometrium) collected intrasurgically and blood samples drawn from 53 women (age 39 to 52 years) with uterine myomas were thoroughly analyzed. In the study group, blood Cd concentration ranged from 0.33 to 3.5 μg/L. Cd concentration in leiomyoma tissues was twice as low [corrected] as that in surrounding myometrium (0.047 and 0.075 μg Cd/g [corrected] wet tissue, respectively), albeit the difference was not statistically significant. Cd concentrations in blood significantly correlated with Cd concentrations in tissues (leiomyoma and surrounding myometrium). The measurement of ER expression showed no difference between leiomyoma tissues and surrounding myometrium. The statistical analysis showed a significant correlation between ER expression and Cd concentration in both tissues under study. An additional statistical analysis (path analysis) demonstrated the correlation of uterine tissue levels of Cd and ER expression. However, there was no association between ER expression in both tissues and E(2) level in serum. Our results suggest a metalloestrogenic effect of Cd by way of ER stimulation in the uterus.

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The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl3. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.