| Objective: Polybrominated Diphenyl Ethers(PBDEs),brominated flame retardants,are widely added in a range of commercial products,textiles,coatings,furniture,mobile phones et al.included.PBDEs have been produced in large quantities and can be released from the products into the environment to become ubiquitous environmental endocrine disruptors(EDCs).Since they are capable of persistence,lipophilicity,bioaccumulation and biomagnifications,PBDEs have profound influences.Thus,the international community has attached great importance to the adverse effects of PBDEs on biota.So far,many countries and regions have restricted or banned their applications,while our country still produces and uses large amounts of Decabromodiphenyl Ether(DBDE).At present,the results of domestic and overseas studies on the effects of intrauterine PBDEs exposure on thyroid functions are controversial and there are no precise conclusions in animal experiments to explain this.In addition,there are few studies on the impacts of intrauterine exposure of PBDEs on the thyroid functions of offspring.Furthermore,the research on its influences on the thyroid functions of successive generations has almost not been reported,and the mechanism is unknown.Given that,this study aimed to establish an intrauterine exposure model of PBDEs in SD rats to observe whether it would affect the thyroid functions and morphology,and fasting glucose in offspring,and explore its potential mechanism.Methods: Thirty SPF female Sprague-Dawley(SD)rats,aged 4 weeks,were permitted to acclimate in SPF environment for 1 week,then we randomly divided them into three groups(large and low dose group and control group)and labeled(HD,LD and Con groups).From 5 weeks of age,three groups of female dams were respectively administered either pharmacologic grade corn oil as a vehicle or DBDE at 100 or 1000 mg/kg bw(decabromodiphenyl ether,98% purity;Sigma,America)by oral.The female rats were weighed weekly to adjust the exposure doses.After 3 consecutive weeks of exposure,two females were arranged with one male(without any treatment).And we examined vaginal smears every morning for the presence of sperm.The day of spermpositive vaginal smears was considered as day 0 of gestation(GD0).Then pregnant rats were kept separate from males and females continued to the treatment above until the first generation of birth.None of offspring rats were exposed DBDE directly,all of them were placed with males at 8 weeks of age to propagate the next generation.The offspring were weaned on PND22 and ten offspring from each group were sacrificed on postnatal day(PND)40 and their weights were recorded;the fasting glucose was detected(blood glucose test strips)and trunk blood was collected.And the thyroid glands were frozen at –80°C for histological investigations,including hematoxylin and eosin(HE),Masson’s Trichrome and immunofluorescence.Moreover,the acquired serum samples were frozen at –80°C for measurement of circulating concentrations of free thyroxine(FT4),total thyroxine(TT4),thyroid stimulating hormone(TSH),thyroglobulin antibody(Tg Ab),transthyretin(TTR)and insulin.Results: On PND40,the body weight of F1 and F2 offspring rats treated with DBDE has no significant changes(P>0.05).The decline of the follicular diameter of the thyroid gland in the first generation showed a significant difference between the 1000mg/kg DBDE treatment group and control group(P ﹤ 0.05).We found that vacuolated changes occurred in the center of the hepatic lobule,and the internal lobular tissue was sparse in F1 offspring rats treated with1000mg/kg DBDE.Compared to the control group,the first generation of rats in 1000mg/kg DBDE treatment group displayed a significant higher proportion of collagen fibrils of the thyroid gland(P﹤0.05).However,above significant differences was not found between both treatment groups and control group in the second generation(P>0.05).Among thyroid follicles of the 1000mg/kg DBDE treatment group in the initial generation existed T and B lymphocyte infiltration showed by immunofluorescence.Moreover,the FT4,TT4 and TTR levels in serum of the first generation were significantly lower in the 1000mg/kg DBDE treatment group than in control group(P<0.05),while the changes of TSH and Tg Ab concentrations were not significant(P>0.05).Fasting glucose and serum insulin levels in rats of the first generation significantly increased in the 1000mg/kg DBDE treatment group than that in control group(P<0.05).And we detected no significant changes between the 100mg/kg DBDE treatment group and control group in follicular diameter and proportion of collagen fibrils of thyroid gland as well as fasting glucose,FT4,TT4,TSH,Tg Ab,TTR and insulin concentrations in serum(P>0.05).As for the second generation,none significant changes was found in any treatment groups.Conclusion: Intrauterine exposure of PBDEs have some adverse effects on thyroid histomorphology and function,and hypothyroxinemia occurs.Insulin resistance also occurs in F1 infants on PND40.However,effects on thyroid morphology have not been found in F2 generation pups,nor did the thyroid function and glucose metabolism. |
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