| Orgnao-tin Compounds were wildly used as pesticide, preservative, bactericide, stabilizer and additive. The environmental of the earth was seriously polluted by organo-tin compounds, especially waters. The organo-tin compounds can be absorbed by body through respiratory passages, digestive canal and skin. Tributyltin (TBT) was an important kind of the compounds. Many studies discovered that TBT have immunotoxicity, neurotoxicity and reproduction toxicity. The present studies about organo-tin compounds in which the exposure dose were high, and few studies on offspring.Objective:To explore the effects of low-dose TBT exposure during gestation and lactation of KM mice on the development and reproductive system. And to explore the possible effects to the human offspring.Methods:The clean healthy adult Pregnant KM mice were randomly divided into 4 groups, 6 in each group, they were given doses of TBT (100,10,1,0μg/kg) by gavage from days 6 of gestation to the end of lactation. Accounting the number of offspring, male and female number, body weight of the newborn when the mice were born, checking the abnormality and death number. Weighing the body weight of the offspring on postnatal day(PND) 1,3,5,7,14,21. Examining the eye opening on PND12, the orchiocatabasis on PND13, the vagina opening on PND20 and the foreskin separate on PND28. weighing the body weight each week after ablactation and calculate the net increase of body weight each muose. Measuring the Righting Reflex and Cliff-drop Aversion Reflex on PNDs 1,3,5,7,9,14.On PND49,10 male and female offspring mice were randomly selected in each group and killed after weighed and trunk blood was collected. The liver, spleen, kidney, thymus, testicle, epididymis or metra and ovary were weighed for account of viscera coefficient. The concentration of estrogen (E2) in serum and testosterone (T) in serum and testicle were measured with radioimmunoassay. The protein expression of CYP1A2,2C6 in liver were examined with western-blotting. The sperm activity, number of sperm, rate of teratosperm and pathology of testicle were measured in PND49 and PND152.Results:The effects of TBT exposure to pregnancy mice:Comparing to the control group, the pregnancy mice body weight gain was significantly lower in 100μg/kg group(P< 0.01).The effects of TBT exposure to the outcome of pregnancy:There were no significantly differences in average litter number, mortality during lactation and the sex ratio between treatment groups and control group(P> 0.05).The effects of TBT exposure to the development of offspring:Comparing with the control group, the eye opening time were significantly delayed in treatment groups. The Cliff-Drop Aversion Reflex in PND7 of treatment groups and the 1μg/kg and 100μg/kg groups in PND3 and the righting reflex time of 10μg/kg and 100μg/kg groups were significantly delayed than the control group. The body weight of treatment groups in PNDs 3,5,21 and 10μg/kg group in PND1 were significantly lower than the control group. The weight gain of the 100μg/kg group during PND1-3 and the 10μg/kg and 100μg/kg groups during PND14-21 were significantly lower than the control group (P<0.05,P<0.01)The effects of TBT exposure to the reproductive system of female:Comparing with the control group, the vagina opening and menarche were significantly ahead in treatment groups, and the body weight when menarche of the offspring was significantly lower (P<0.01). On PND49, the concentration of estrogen in serum of 100μg/kg group was significantly higher than the control group(P<0.01), the body weight of treatment group in PND21 was significantly lower than the control group, the body weight gain of 10μg/kg group during PND21-49 was significantly higher than the control group(P<0.01,P<0.05), the weight of spleen and its organ coefficient of 10μg/kg group were significantly lower than the control group, the weight of kidney and its organ coefficient of 1μg/kg and 100μg/kg groups were significantly higher than the control group(P<0.01,P<0.05). The body weight of 100μg/kg in PNDs56,70,152 and its body weight gain during PND49-63, PND49-152 were significantly lower than the control group, the body weight of 10μg/kg in PND84 was significantly higher than the control group(P<0.01,P<0.05). The weight of ovary of 100μg/kg group in PND152 was significantly lower than the control group(P<0.05). The rate of abnormal estrous cycle of treatment groups were significantly higher than the control group(P< 0.05).The effects of TBT exposure to the reproductive system of male mice: Comparing with the control group, the body weight of 100μg/kg group in PNDs21,42, and the body weight of 10μg/kg group in PND42, and the body weight of treatment groups in PND49 were significantly lower(P<0.05,P<0.01). The body weight gain of 10μg/kg group during PND35-42 and 1μg/kg group during PND42-49 were significantly lower(P<0.05,P<0.01). The orchiocatabasis and foreskin separation of treatment groups were significantly delayed than the control group, the rate of teratosperm of 1μg/kg and 10μg/kg groups was significantly higher than the control group, the testicle coefficient of 100μg/kg group was significantly higher(P<0.05, P <0.01). On PND49, there were a decrease trend of account of sperm and the level of T in serum with the dose increase, there was a increase trend of T level in testicle with the dose increase, but there were no significant statistically. The ratio of E2/T in serum of male offspring was significantly higher than the control group, otherwise, the rate of E2/T and the level of E2 in testicle were significantly lower than the control group(P<0.05,P<0.01). The body weight of 100μg/kg group in PND63 was significantly lower than the control group, the body weight gain of 10μg/kg group during PND77-152 and 1μg/kg and 10μg/kg groups during PND49-152 were significantly higher than the control group(P<0.01). On PND152, the spleen weight of 100μg/kg group male offspring was significantly higher than the control group, the kidney weight and its organ coefficient were significantly lower than the control group(P<0.05,P<0.01). The weight of testicle and the organ coefficients of liver and spleen were significantly higher than the control group(P<0.05,P<0.01). The level of E2 in serum of the adult male offspring and the T level in testicle of 1μg/kg group, and the ratio of E2/T in testicle of 10μg/kg and 100μg/kg groups were significantly lower than the control group, the account of sperm and sperm activity were significantly lower than the control group(P<0.05,P<0.01). On PND152, there were no significantly difference in the level of T in serum and the ratio of E2/T in testicle and the rate of abnormal sperm between the treatment groups and control group(P>0.05).Conlusions:we can get the conlusions as follows from the stduty:1. Low dose TBT exposure in gestation and lactation has maternal toxicity to the pregnant mice, it can induce the body weight gain decrease. TBT has endocrine disrupt effect to the offspring, it can affect the development of the offspring, TBT can induce the female offspring neoteny.2. TBT have organ toxicity and reproductive toxicity to the offspring. The weight of ovary of the adult female offspring decrease, and the estrous cycle of adult female offspring were disorder. The testicle coefficient of adolescence male offspring was increase, the quality of sperm was low.3. TBT may has different effects between male and female offspring. TBT can induce the body weight of adult male increase, in contrary, the body weight of adult female was decreased. The E2 level in serum of female was rised, otherwise, the male was reduced. TBT can induce the female neoteny, cause the male lateness.4. According to this study, we consider that WHO under estimate the potential hazardous of TBT when they rule the tolerable daily intake of TBT. The mice were exposed to EDCs during peripartal, checking the time of vagina opening and menarche, this may be a simple, economy, easy progress and credibility method to assess the EDCs.
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