The Effects And Mechanism Of The Taurine On Placenta Damage And Embryonic Developmental Toxicity By Cadmium Chloride In Rats

Objective: Cadmium, one of the most of dangerous heavy metals, had been proved to have toxic effects to several kinds of organs and tissues of laboratory animals and human beings, especially reproductive system, which was one of the most sensitive tissues to the toxic effects of Cadmium. It had been demonstrated that various procedures were involved in cadmium-induced reproductive toxicity, such as oxidative stress, interaction between cadmium and calcium, cadmium and MT, inhibition of enzyme activity. But few studies were concerned about the prevention on cadmium- induced reproductive toxicity, and by which mechanisms it worked. Taurine( Tau) is aβ- amino acid. It is also a kind of sulfur-bearing amino acid found in all tissues of most animal species and the most abundant free amino acid in many tissues. It has widespread biological effect. It had been characterized that Tau could enhance the defense system of antioxidation of body. This research use rat model to study placenta histological feature by level of microscopy, optical microscopy and electronic microscopy, e-NOS and AKP expression in placenta, the level of E2 and P, embryonic development. The objective of this research was to demonstrate whether Tau could antagonize cadmium-induced placenta damage and embryonic developmental toxicity, and by which mechanisms it worked. This study also provides the evidences to the prevention and treatment of cadmium- induced toxicity in pregnant period.Methods: 50 SD rats which weigh 240～270g were randomly divided into: Control group (A); CdCl2 group (B); 100mg/kg.d Tau group (C); 400mg/kg.d Tau group (D); 800mg/kg. d Tau group (E). Groups BCDE were given 40mg/L cadmium chloride through hydroposia, Group A were given distilled water. Groups C D E were given Tau at the dosage of 100, 400, 800mg/kg.d through oral at 9:00am for 20days. Distilled water was given at the same dosage in groups AB. During the period, we observed the growth of rats and measured the weight every week. 20days later rats of each group were obtained 5ml blood from the hearts, and the content of cadmium, E2, P in the blood serum was evaluated. Then all the rats received caesarean operation. We selected 20 placentas for measure in every group. The surroundings is germfree. HE and electronic microscopy were used to observe the changes of placenta morphology; immunohistochemistry was used to measure e-NOS, AKP expression. We selected 20 newborns randomly. Their body weight, body length and tail length were measured. The content of cadmium in placentas and fetus livers were evaluated. The datum were analyzed by statistics software SPSS12.0 include Q-test, one-way-ANOVA and analysis of linear correlation.Results1 General state of health: Cadmium chloride had a little influence on maternal food and water intake at the experimental condition. The SD rats of group B had some abnormal appearance, such as listless, less move, liking pile up to sleep. After given Tau, the conditions had improved.2 To compare maternal body weight, no significant difference shows among groups early days(P>0.05);the body weight of other groups is lower than A group during 14-20 days(P<0.05); the body weight of E group is higher than B group (P<0.05); no significant difference shows between CD groups and B group (P>0.05), but has rise tendency.3 Placenta morphology:3.1 Observing minute structure by the light microscope: pathology change of placenta in B group was the most evident. It is obvious that chronic non-special inflammation as fibrotic putrescence and lymphocyte and plasm cell soakage in labyrinth layer and floor layer , villi structures were disordered. Compared to B group, pathology change of placenta in CDE groups had obviously relieved. It is very similar between E group and A group.3.2 Observing by the electron microscope: microvilli around the trophoblast were shorter and less, mitochondrion was swollen and decreased in number, rough endoplasmic reticulum was distended and ribosomal number on membrane decreased. The alteration would less and less severe with the increase of the dose of Tau. Microvilli around the trophoblast were recovered the earliest.4 Immunity result: If syneytiotrophoblast intracytoplasm appears buffy grains, it is the masculine cell. The e-NOS, AKP expressions of B group are significantly lower than A group(P<0.01); The e-NOS, AKP expressions of DE groups are higher than B group(P<0.05); no significant difference shows between C group and B group(P>0.05).5 The P, E2 levels of B group are significantly lower than A group(P<0.01); the P, E2 levels of DE groups are significantly higher than B group(P<0.01); no significant difference shows between C group and B group(P>0.05).6 Compared with A group, the content of cadmium in blood serum, placenta and fetus liver of B group are all significantly higher(P < 0.01); compared with B group, the content of cadmium in blood serum and placenta of CDE groups are all lower(P<0.05). the content of cadmium in placenta and fetus liver of all groups shows correlation with blood serum cadmium(P<0.05).7 Fetus body weight, body length and tail length and placenta weight of B group are significantly lower than A group(P<0.01); compared with B group, placenta weight and fetus body weight of CDE groups increase to some extent(P<0.05), but still to remain lower than A group(P<0.05); fetus body length and tail length of E group are higher than B group(P<0.05).Conclusion1 The model of cadmium-induced reproductive toxicity and embryonic developmental toxicity was successfully established in our experiment. Placenta structure is damaged; enzyme expression in the placenta is diminished; the levels of E2, P are descending. In a word, placenta is one of the target organs.2 Embryon developmental abnomaly in that placenta barrier function breakdown. Liver is a major detoxicating place, fetus liver cadmium content could reflect blood serum cadmium content.3 Taurine could antagonize cadmium-induced reproductive and embryonic developmental toxicity, and they have dose-effect relation.4 The mechanisms of taurine is possibly through enhanced antioxidant activity, increased cadmium excretion, decreased placenta cadmium content, restored enzyme expression in the placenta and maintained serum sex hormone level.