Effect of Manganese Exposure on the Reproductive Organs in Immature Female Rats

Manganese (Mn(2+)) is a trace element that is essential for normal physiology, and is predominantly obtained from food. Several lines of evidence, however, demonstrated that overexposure to MnCl(2) exerts serious neurotoxicity, immunotoxicity and developmental toxicity, particularly in male. The present study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of MnCl(2) on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to MnCl(2) (MnCl(2) ∙ 4H(2)O) dissolved in drinking water for 2 weeks. The animals were sacrificed on PND 35, then the tissues were immediately removed and weighed. Histological studies were performed using the uteri tissue samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body weights of the experimental group animals were not significantly different from those of control group animals. However, ovarian tissue weights in 1 mg and 3.3 mg MnCl(2) dose groups were significantly lower than those of control animals (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose MnCl(2) groups were significantly lower than those of control animals (p<0.01), while the 1 mg MnCl(2) dose and 10 mg MnCl(2) dose failed to induce any change in uterine weight. Similarly, only 3.3 mg MnCl(2) dose could induce the significant decrease in the oviduct weight compared to the control group (p<0.05). Non-reproductive tissues such as adrenal and kidney failed to respond to all doses of MnCl(2) exposure. The uterine histology revealed that the MnCl(2) exposure could affect the myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group. Serum FSH levels were significantly decreased in 1mg MnCl(2) dose and 10 MnCl(2) mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl(2) dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that MnCl(2) exposure is capable of inducing abnormal development of reproductive tissues, at least to some extent, and altered gonadotropin secretions in immature female rats. Combined with the well-defined actions of this metal on GnRH and prolactin secretion, one can suggest the Mn(2+) might be a potential environmental mediator which is involved in the female pubertal process.