| Melamine(MA)and cyanuric acid(CA)is widely used for the manufacture of plastics,tableware,and disinfector.Therefore people are easily in touch with melamine and cyanuric acid in daily life.In addtion,numerous dogs,cats and infants were reported to fall ill even died because of MA illegally added into pet foods or milk powder.These occurrences evoke more and more people to concern the toxicity of MA and MC.Previous studies on toxicity of MA and MC mainly focused on urinary and male reproductive systems.Crystals in kidney and testes,destruction of blood-testis barrier,damage of spermatogonium and seminiferous tubules were observed.However,few studies have investigated the effects of MA or MC on female reproductive organs.In this study,we investigated ovarian lesions in young female rats after they were exposed to melamine or melamine-cyanuric acid mixture,with the aim of understanding melamine toxicity in greater detail.Seventy SD rats were randomly divided into seven groups:MA high-dose group(40mg/kg·bw),MA moderate-dose group(20mg/kg·bw),MA low-dose group(10mg/kg·bw),MC high-dose(20mg/kg·b w MA +20mg/kg·bw CA),MC moderate-dose(10 mg/kg·bw MA+1 0mg/kg·bw CA),MC low-dose(5mg/kg·bw MA+5mg/kg·bw CA)and control group(same volume of corn oil).All the rats were orally administrated once a day for 28 consecutive days.The weight of body,ovaries and uterus,estrus cycle,estradiol and progesterone in serum,pathology of ovaries,apoptosis of granulosa cells detected,the mRNA level of steroidogenesis and antioxidant enzyme were evaluated after the experiment finished.Reduction of food and water intake,rough hair and depression were found after rats exposure to 20 and 40 mg·(kg·d)-1 MC groups.The weight of rats in the 20 and 40 mg·(kg·d)-1 MC groups were decreased obviously(P<0.01),the relative weights of ovaries and uterus were significantly decreased(P<0.01).The duration of estrous cycle was significantly shortened in the 20 and 40 mg·(kg·d)-1 MC groups than the control(P<0.05),and there were no differences in other groups.The serum E2 level in the 40 mg·(kg·d)-1 MC group and the serum P level in the 20 and 40 mg·(kg·d)-1 mixture groups were significantly decreased(P<0.05).The morphological changes were observed in the ovary and renal tubule,brown crystals were,found in the distal tubules,interstitial hyperplasia;necrosis of oocyte nucleus and granulosa cells,thin layers of granulosa cells were observed in the groups exposed to 40 mg(kg·d)-1 MA group and MC treated-groups.The exposure groups had higher numbers of atretic follicles,and the 40 mg·(kg·d)-1 MA group and MC groups showed a significantly higher number of atretic follicles than the control group(P<0.05).The expression of SOD1 mRNA level was significantly lower in the 40 mg·(kg·d)-1 MA group and MC treated-groups(P<0.05),the SOD2 mRNA levels were obviously higher in the MC groups than in the controls(P<0.05).The GPX1 mRNA levels in the 20 and 40 mg·(kg·d)-1 MA and MC groups and the GPX2 mRNA level in the MC group were significantly lower than the control group(P<0.05).The mRNA expression levels of 17?-HSD ? and 17?-HSD ? in the 20 and 40 mg·(kg·d)-1 MA and MC groups were significantly lower than in the control group(P<0.05).The P450scc mRNA level in the 40 mg·(kg·d)-1 MC group was significantly lower(P<0.05).The number of TUNEL-positive cells increased with increase dose of MA or MC.The percentages of apoptotic cells in the 40 mg·(kg·d)-1 MA group,20 and 40 mg·(kg·d)-1 mixture group were significantly greater than the control group(P<0.05).The damage of mitochondria in oocyte and chromatin condensation in granulosa cells were observed 40 mg·(kg·d)-1 MC group by ultrastructure detection.These results indicated that MA and MC could caused the damage of ovary,reduction the serum level of estradiol and progesterone,the damage of ovary was related to the apoptosis of granulosa cells and oxidative stress,the reduction of estradiol and progesterone was related to inhibition of the activity of steroidogenesis enzyme. |
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