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Updated: Apr 12, 2026

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Effect of manganese exposure on the reproductive organs in immature female rats
Soo In Kim1, Yeon Seok Jang1, Seung Hee Han1
1Dept. of Green Life Science, Sangmyung University, Seoul 110-743, Korea.
Abstract:
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 MnCl2 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 MnCl2 on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to MnCl2 (MnCl2 ∙ 4H2O) 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 MnCl2 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 MnCl2 groups were significantly lower than those of control animals (p<0.01), while the 1 mg MnCl2 dose and 10 mg MnCl2 dose failed to induce any change in uterine weight. Similarly, only 3.3 mg MnCl2 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 MnCl2 exposure. The uterine histology revealed that the MnCl2 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 MnCl2 dose and 10 MnCl2 mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl2 dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that MnCl2 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.
Insights
Manganese chloride (MnCl2) exposure in young female rats reduced ovarian and uterine weights and altered reproductive hormone levels. This suggests MnCl2 may interfere with female pubertal development.
Area of Science:
- Toxicology
- Reproductive Biology
- Environmental Health
Background:
- Manganese (Mn2+) is an essential trace element, but overexposure to manganese chloride (MnCl2) can cause toxicity.
- Previous studies indicate MnCl2 toxicity affects neurodevelopment and the immune system, particularly in males.
- The impact of MnCl2 on female reproductive system development requires further investigation.
Purpose of the Study:
- To investigate the effects of varying MnCl2 doses on the reproductive organs of immature female rats.
- To assess potential alterations in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.
- To determine if MnCl2 exposure impacts reproductive tissue development and histology.
Main Methods:
- Immature female rats were exposed to 0, 1.0, 3.3, or 10 mg/kg/day MnCl2 in drinking water for two weeks.
- Ovarian, uterine, and oviduct weights were measured post-sacrifice.
- Uterine histology and serum LH and FSH levels (via ELISA) were analyzed.
Main Results:
- MnCl2 exposure significantly decreased ovarian weights at 1.0 and 3.3 mg/kg/day doses.
- Uterine and oviduct weights were significantly reduced at the 3.3 mg/kg/day dose.
- Histological analysis indicated MnCl2 affected myometrial cell proliferation, and serum FSH levels decreased, while LH levels increased at specific doses.
Conclusions:
- MnCl2 exposure can induce abnormal reproductive tissue development and alter gonadotropin secretion in immature female rats.
- These findings suggest Mn(2+) may act as an environmental mediator influencing female pubertal processes.
- Further research is warranted to understand the full implications of MnCl2 exposure on female reproductive health.

