Study On Reproductive Toxicity Of Dibulytin Dilaurate In Female Mice

Objective After the ozone layer break and green house effect, the environmental estrogen is becoming one of the major problems of environment. As a kind of familiar environment hormone, organotin exists with various forms, and it primarily used to stabilize polyvinyl chloride (PVC), defend the dirty coating, as insecticide and fungicidal etc. The health effects of DBTD are irritating to skin and mucous membrane,and its effects on digestive, nerval, immune, endocrine and reproductive systems. In order to elucidate the effects of DBTD on reproductive toxicity, the activities of enzyme in serum, concentration of E2 and P in serum were measured, and damages DBTD did to uterus and ovary were also observed. The modality and the development of embryo mice were also observed to find the effects of DBTD on offspring. Methods 100 female healthy Wister mice were purchased from animal center of XinMin faculty. Body weight of the mice is(200-240)g. And 60 mature male mice (only to mating). The female mice were classified into control group randomly N=20, DBTD exposed group. Exposed dose was 2.5mg/kg body wt (1/72LD50) N=25, 10mg/kg body wt (1/18 LD50) N=25, 20mg/kg body wt (1/9 LD50) N=30. Female mice were given DBTD by gastric intubation at 0, 2.5, 10, or 20 mg/kg and the volume of liquor within 1-2ml, 6d/w, consecutively for 8w. At the end of 5^th week take out some of female mice randomly (control 10, 1/72LD50 15, 1/18 LD50 15, 1/9 LD50 20), male and female mice were roomed together wyth male 1 and female 1, and the rest mice (without mating) went on giving DBTD until the end of 8th. The pregnant mice were consecutively given DBTD for 18 days. On day 18 after the mice were pregnant, the female mice were sacrificed and their offsping were examined, pregnancy rate of female mice, live fetus per litter and absorption ratio of embryo, average weight of fetus, the sex ratio, the malformation of fetus were calculated, and observed the development of bone on fetus. And in the rest female rice (without mating), E2 and P concentration and enzyme activities in serum and the content of tin in uterus, ovary and liver were measured, and observed the pathologic changes of uterus and ovary in mice. Statistics analyses of quantitative data were conducted using variance analyses. Categorical data were analyzed by Chi-square test. Results 1. Effects of DBTD on the body weight of female mice: The body weight increased slowly in control and 1/72LD50 group while the weight of body significantly decreased in 1/9LD50 group,compared with control group (P<0.05). And there is no change in 1/18LD50 group. 2. Effects of DBTD on enzyme activities of female mice in serum: The activities of enzyme NO and NOS increased with the dose of DBTD in each exposure group, and compared with control group and each exposure group (P<0.05). 3. Content of tin in uterus, ovary and liver: In 1/18LD50 and 1/9LD50 dose group, it can cumulate in uterus and ovary, especially in liver (P<0.05). 4. Effects of DBTD on E2 and P concentration in serum of mice: Theconcentration of E2 in serum decreased in different exposed group。E2 concentration in serum from 1/72LC50 to 1/9LC50 group mice was significantly lower than that of control mice and the concentration of P in serum kept in normal level, indicating that DBTD can inhibit the secretion of E2 (P<0.05)and can not affect the secretion of P in mice. 5. Pathologic changes of uterus and ovary tissue in mice: The structure of uterus was damaged from mice in exposed group, especially in 1/9LD50, the putrescence appeared in the endothecium mucous membrane of uterus. 6. Effects of DBTD on the pregnant mice: The mating rate of female mice which have been exposed to DBTD, the pregnancy rate of female mice, ratio of absorption were significantly increased from that of control group(P<0.05). 7. Effects of DBTD on the fetus: The number of live fetus per litter, average weight of fetus, the fetus sex ratio (female:male) in 1/18LD50 and 1/9LD50 group decreased with the increasing of exposure dosage. DBTD can affect the development of bone in the fetus, and induce malformation of fetus. In 1/18LD50 and 1/9LD50 group, the malformation of fetus increased with the increasing of exposure dosage. Conclusion Results from the present research showed that long-term exposure to DBTD can cause pathologic changes of uterus from female mice, increasing activities of enzymes of ALP, GGT and GPT in serum, the decreasing of activities of enzymes of NO and NOS and concentration of E2 and P hormone in serum. Female mice after exposure to DBTD mated with male mice, absorption ratio of female mice and malformation ratio of fetus...