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. 2016 Feb 11;11(2):e0149063.
doi: 10.1371/journal.pone.0149063. eCollection 2016.

Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid

Jiarui Sun  1 , Xinchen Zhang  1 , Yinan Cao  1 , Qiling Zhao  1 , Endong Bao  1 , Yingjun Lv  1
Affiliations

Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid

Jiarui Sun et al. PLoS One. .

Abstract

Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Effect of cyanuric acid (CA) on female rats.
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: CA group versus control group. Ovarian sections are stained with hematoxylin and eosin.
Fig 2
Fig 2. Body weights of rats after exposure to different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 3
Fig 3. Gross pathological and histopathological changes of kidneys.
Hematoxylin-eosin staining illustrating the gold-brown crystals (black arrow), cellular casts (blue arrow) and compensatory expansion (red arrow).
Fig 4
Fig 4. Absolute and relative ovary and uterus weights of rats exposed to different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 5
Fig 5. Estrous cycles of rats exposed to different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 6
Fig 6. Serum levels of estrogen and progesterone of rats exposed to different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 7
Fig 7. Photomicrographs of ovary sections.
Hematoxylin-eosin staining illustrating the necrosis of granulosa cells (white arrows).
Fig 8
Fig 8. Numbers of atretic follicles in ovaries after rats were treated with different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 9
Fig 9. Apoptotic cells in rat ovaries detected by TUNEL staining after the rats were exposed to different doses of melamine (MA) and melamine and cyanuric acid (MC).
TUNEL-positive cells were found in the granulosa cells (black arrows).
Fig 10
Fig 10. Percentages of apoptotic cells in ovaries after rats were exposed to different doses of melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 11
Fig 11. mRNA expressions of antioxidant enzymes in the ovaries of rats exposed to melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
Fig 12
Fig 12. mRNA expression levels of genes associated with steroidogenesis in ovaries of rats exposed to melamine (MA) and melamine and cyanuric acid (MC).
Values are expressed as means ± SD, n = 5. *P < 0.05, **P < 0.01: MA group versus control group and MC group versus control group.
See this image and copyright information in PMC

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