The effect of repeated cadmium oral exposure on the level of sex hormones, estrous cyclicity, and endometrium morphometry in female rats

Abstract

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.

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

“…In addition, subacute Cd administration led to Cd accumulation and the induction of oxidative stress in rat ovaries and uterus [29,31]. The results of our previous work indicate that subacute (30-day) exposure to Cd leads to histopathological changes in the ovaries and in the uterus, as well as disturbances in the concentrations of circulating steroid hormones, suggesting an antiestrogenic effect, which was associated with abnormalities in the estrous cycle in female rats [24]. Despite that environmental exposure to Cd is lifelong, data on the subchronic or long-term effects of Cd on the uterus is still limited.…”

“…Cd uterus concentration [24]. After a 90-day administration of Cd, its concentration in the uterus increased in a dose-dependent manner and was about three times higher than that after a 30-day administration [24].…”

“…Cd uterus concentration [24]. After a 90-day administration of Cd, its concentration in the uterus increased in a dose-dependent manner and was about three times higher than that after a 30-day administration [24]. Moreover, Cd concentrations in the uterus six months after terminating the exposure were virtually at the same level as at the end of the administration period.…”

“…In humans, Cd accumulates not only in the kidney and liver, but also in the reproductive organs [10][11][12]. To date, many in vivo studies indicate the toxic effects of Cd on female reproductive organs, including the endocrine system, the effects which seem to depend not only on the dose but also on the route of Cd administration [13][14][15][16][17][18][19][20][21][22][23][24]. However, the mechanism of Cd reproductive toxicity has not yet been elucidated completely, and there are still controversies with regard to the estrogen-like effect of this metal.…”

“…Because of disturbed steroid hormone secretion, it is also suggested that the direct effect of Cd on the ovaries or the indirect effect of Cd on the hypothalamus-pituitarygonadal axis should not be excluded. It was proved in in vivo studies that Cd administration leads to histopathological alterations in the ovary (degeneration of the corpus luteum, damaged and less numerous oocytes, and degeneration of granulosa cells) and uterus (an increase in the luminal epithelial height and in the endometrial thickness) [24,[28][29][30]. In addition, subacute Cd administration led to Cd accumulation and the induction of oxidative stress in rat ovaries and uterus [29,31].…”