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

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.

Effects of Cadmium, Lead, and Mercury on the Structure and Function of Reproductive Organs

“…In adult female Wistar rats exposed to cadmium, a statistically significant prolongation of the cycle was noted [ 40 ]. This effect was observed not only by the estrus phase but also by the diestrus phase.…”

“…At the highest dose of cadmium (4.5 mg/kg bw), diestrus was extended, whereas proestrus was shortened although no significant increase in the duration of the cycle length was observed. Histopathological alterations in the ovaries of the cadmium-exposed rats were degeneration of the corpus luteum and damaged and fewer oocytes [ 40 ].…”

Effect of Acute Exposure of Cigarette Smoke on Endometrium Thickness and Number of Ovarian Follicles in Rats

“…They also found that lower dose cadmium significantly increased the thickness of endometrium but in higher dose cadmium they found noticeable endometrial atrophy, therefore it concluded that cadmium can have both anti-estrogenic and estrogenic effect. 11 In this study, we found no significant difference in the control and experimental group, we theorize that this might be because we used lower dose and short amount of exposure time only. We also use whole smoke exposure thus there are many different chemical that might influenced the result of this study.…”

“…10 Based on previous study, it seems that the effect of cadmium exposures varies based on the dose and routes of administration. 11 Zhang, et al, conducts research on rat's endometrium given intraperitoneal cadmium and found thickening of the endometrium and myometrium, the study also stated that intraperitoneal cadmium causes inflammation in the endometrial stroma of the rats. 12 Da Costa et al, also conducted an experimental research on cadmium exposures by oral routes but they did not found any significant difference in the thickness of endometrium, however they found decrease of myometrium thickness in the experimental group.…”

Serum Sex Hormonal Responses to Acute Oral Cadmium Exposure of Male Wistar Rats

“…Chronic Cd exposures has been reported to disturbed reproductive endocrine function, cause testes degeneration, decrease testicular mass [17][18][19], and decreased spermatozoa mobility [20] in male rats. Studies in female rats showed Cd accumulates in the female reproductive organs [9,14,[21][22][23][24]. In vivo studies have shown Cd administration to cause histopathological alterations in the ovary and uterus that include corpus luteum and granulosa cells degeneration, deceased oocytes population, increased luminal epithelial height and endometrial thickness [1,25,26] and disturbances in the concentrations of…”