孕哺期十溴联苯醚染毒对子鼠甲状腺激素水平的影响
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摘要
[目的]探讨母鼠孕期和哺乳期十溴联苯醚(BDE209)染毒对子鼠发育期和成年期血清甲状腺激素(TH)水平的影响。[方法] 30只无特定病原体级8周龄F0代雌性昆明小鼠自交配成功后,随机分为对照组、低、高剂量染毒组,每组10只。对照组母鼠灌胃0.01 L/kg花生油(以体重计,后同),染毒组母鼠以50、300μg/kg灌胃染毒BDE209,连续染毒至F1代子鼠出生后第21天(PND21,发育期),建立F0代孕期至哺乳期染毒模型。30只8周龄F1代雌性昆明小鼠自交配成功后,分别经口灌胃0.01 L/kg花生油和50、300μg/kg BDE209,连续染毒至F2代子鼠PND21,建立F1代孕期至哺乳期染毒模型。在F1、F2代子鼠PND21和PND60(成年期),测量小鼠体重,同时采用直接化学发光法检测外周血血清中总四碘甲状腺原氨酸(T4)、游离四碘甲状腺原氨酸(FT4)、总三碘甲状腺原氨酸(T3)、游离三碘甲状腺原氨酸(FT3)水平。[结果]与对照组相比,低、高染毒组F0、F1代母鼠体重和产仔数均出现了下降;低、高染毒组F1、F2代子鼠在PND21时,体重均出现了下降(均P<0.05)。与对照组相比,低、高染毒组F1代子鼠在PND21时,T4各升高了21.1%、37.2%;在PND60时,高染毒组T4升高了23.2%(均P<0.05)。与对照组相比,低、高染毒组F1代子鼠在PND21时,FT4各升高了22.7%、53.9%;在PND60时,高染毒组FT4升高了16.7%(P<0.05)。与对照组相比,高染毒组F1代子鼠在PND21时,T3升高了22.8%;PND21高染毒组F1代子鼠FT3升高了33.8%(均P<0.05)。与对照组相比,低、高染毒组F2代子鼠在PND21时,T4各升高了19.5%、48.2%;在PND60时,低、高染毒组T4各升高了19.2%、29.2%(均P<0.05)。与对照组相比,低、高染毒组F2代子鼠在PND21时,FT4各升高了27.4%、65.3%(P<0.05);在PND60时,高染毒组F2代子鼠FT4升高了32.5%(P<0.05)。与对照组相比,低、高染毒组F2代子鼠在PND21时,T3各升高了10.8%、19.8%;高染毒组F2代子鼠在PND21时,FT3升高了20.2%(均P<0.05)。[结论]孕哺期BDE209暴露具有TH干扰毒性,会引起子代发育期和成年期TH水平出现紊乱。
[Objective] To evaluate the effects of exposure to decabromodiphenyl ether(BDE209) of mothers during pregnancy and lactation on serum thyroid hormone(TH) concentrations of offspring mice at puberty and adulthood.[Methods] Thirty specific pathogen free female Kunming mice of 8 weeks old were used as F0 generation and randomly divided into control,low exposure,and high exposure groups after mating,with 10 mice in each group.The control group was fed with peanut oil at 0.01 L/kg(in terms of body weight,thereafter),and the exposure groups were given BDE209 at 50 and 300 μg/kg by intragastric administration once a day until postnatal day 21(PND21,puberty) of F1 generation offspring mice,establishing a F0 generation exposure model from pregnancy to lactation.Then,thirty female Kunming mice of the F1 generation of 8 weeks old were randomly divided into control,low exposure,and high exposure groups after mating and received the same treatments as the F0 generation until PND21 of F2 generation offspring mice,establishing a F1 generation exposure model from pregnancy to lactation.The body weights of mice were measured on PND21 and PND60(adulthood) of F1 and F2 generation offspring mice.The serum levels of total thyroxine(T4),total triiodothyronine(T3),free thyroxine(FT4),and free triiodothyronine(FT3) were measured by direct chemiluminescence immunoassay at the same time points.[Results] Compared with the control group,the body weights and the litter sizes of the F0 and F1 generation mother mice were significantly decreased in the low and high BDE209 exposure groups;the body weights of the F1 and F2 generation offspring mice in the low and high BDE209 exposure groups significantly decreased on PND21(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T4 concentrations of the F1 generation offspring mice by 21.1% and 37.2% on PND21,respectively;the high BDE209 exposure significantly increased the T4 concentration of the F1 generation offspring mice by 23.2% on PND60(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the FT4 concentrations of the F1 generation offspring mice by 22.7% and 53.9% on PND21,respectively;the high BDE209 exposure significantly increased the FT4 concentration of the F1 generation offspring mice by 16.7% on PND60(Ps<0.05).Compared with the control group,the high BDE209 exposure significantly increased the T3 and FT3 concentrations of the F1 generation offspring mice by 22.8% and 33.8% on PND21,respectively(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T4 concentrations of the F2 generation offspring mice by 19.5% and 48.2% on PND21 and by 19.2% and 29.2% on PND60,respectively(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the FT4 concentrations of the F2 generation offspring mice by 27.4% and 65.3% on PND21,respectively;the high BDE209 exposure significantly increased the FT4 concentration of the F2 generation offspring mice by 32.5% on PND60(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T3 concentrations of the F2 generation offspring mice by 10.8% and 19.8% on PND21,respectively;the high BDE209 exposure significantly increased the FT3 of the F2 generation offspring mice by 20.2% on PND60(Ps<0.05).[Conclusion] Exposure to BDE209 during pregnancy and lactation has significant toxicity on TH homeostasis,which may lead to disorder in TH level during puberty and adulthood of the offspring.
[Objective] To evaluate the effects of exposure to decabromodiphenyl ether(BDE209) of mothers during pregnancy and lactation on serum thyroid hormone(TH) concentrations of offspring mice at puberty and adulthood.[Methods] Thirty specific pathogen free female Kunming mice of 8 weeks old were used as F0 generation and randomly divided into control,low exposure,and high exposure groups after mating,with 10 mice in each group.The control group was fed with peanut oil at 0.01 L/kg(in terms of body weight,thereafter),and the exposure groups were given BDE209 at 50 and 300 μg/kg by intragastric administration once a day until postnatal day 21(PND21,puberty) of F1 generation offspring mice,establishing a F0 generation exposure model from pregnancy to lactation.Then,thirty female Kunming mice of the F1 generation of 8 weeks old were randomly divided into control,low exposure,and high exposure groups after mating and received the same treatments as the F0 generation until PND21 of F2 generation offspring mice,establishing a F1 generation exposure model from pregnancy to lactation.The body weights of mice were measured on PND21 and PND60(adulthood) of F1 and F2 generation offspring mice.The serum levels of total thyroxine(T4),total triiodothyronine(T3),free thyroxine(FT4),and free triiodothyronine(FT3) were measured by direct chemiluminescence immunoassay at the same time points.[Results] Compared with the control group,the body weights and the litter sizes of the F0 and F1 generation mother mice were significantly decreased in the low and high BDE209 exposure groups;the body weights of the F1 and F2 generation offspring mice in the low and high BDE209 exposure groups significantly decreased on PND21(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T4 concentrations of the F1 generation offspring mice by 21.1% and 37.2% on PND21,respectively;the high BDE209 exposure significantly increased the T4 concentration of the F1 generation offspring mice by 23.2% on PND60(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the FT4 concentrations of the F1 generation offspring mice by 22.7% and 53.9% on PND21,respectively;the high BDE209 exposure significantly increased the FT4 concentration of the F1 generation offspring mice by 16.7% on PND60(Ps<0.05).Compared with the control group,the high BDE209 exposure significantly increased the T3 and FT3 concentrations of the F1 generation offspring mice by 22.8% and 33.8% on PND21,respectively(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T4 concentrations of the F2 generation offspring mice by 19.5% and 48.2% on PND21 and by 19.2% and 29.2% on PND60,respectively(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the FT4 concentrations of the F2 generation offspring mice by 27.4% and 65.3% on PND21,respectively;the high BDE209 exposure significantly increased the FT4 concentration of the F2 generation offspring mice by 32.5% on PND60(Ps<0.05).Compared with the control group,the low and high BDE209 exposures significantly increased the T3 concentrations of the F2 generation offspring mice by 10.8% and 19.8% on PND21,respectively;the high BDE209 exposure significantly increased the FT3 of the F2 generation offspring mice by 20.2% on PND60(Ps<0.05).[Conclusion] Exposure to BDE209 during pregnancy and lactation has significant toxicity on TH homeostasis,which may lead to disorder in TH level during puberty and adulthood of the offspring.
引文
[1]宋琪,司婧,张蕴晖.孕期多溴联苯醚暴露与胎儿发育不良关联的研究进展[J].环境与职业医学,2017,34(12):1105-1110.
[2]朱春艳,安月,钱波,等.三代小鼠十溴联苯醚灌胃染毒对子鼠(F1、F2)学习记忆能力的影响[J].环境与职业医学,2014,31(12):930-935.
[3]CHEN L,HUANG Y,XU Z,et al.Human exposure to PBDEs via house dust ingestion in Guangzhou,South China[J].Arch Environ Contam Toxicol,2011,60(3):556-564.
[4]AKUTSU K,TAKATORI S,NAKAZAWA H,et al.Dietary intake estimations of polybrominated diphenyl ethers(PBDEs)based on a total diet study in Osaka,Japan[J].Food Addit Contam Part B Surveill,2008,1(1):58-68.
[5]FOSTER W G,GREGOROVICH S,MORRISON K M,et al.Human maternal and umbilical cord blood concentrations of polybrominated diphenyl ethers[J].Chemosphere,2011,84(10):1301-1309.
[6]焦扬,邓琳,赵贺,等.北京市海淀区产妇母乳中多溴联苯醚的初步调查[J].环境与健康杂志,2013,30(4):328-331.
[7]张琳,田英,杨先丰,等.上海市某医院新生儿脐带血中多溴联苯醚水平及其对出生结局的影响[J].中华预防医学杂志,2011,45(6):490-493.
[8]ESKENAZI B,FENSTER L,CASTORINA R,et al.Acomparison of PBDE serum concentrations in Mexican and Mexican-American children living in California[J].Environ Health Perspect,2011,119(10):1442-1448.
[9]张洪梅,苏青,罗敏.甲状腺激素缺乏对不同发育时期大鼠脑组织氧化应激指标的影响[J].吉林大学学报(医学版),2010,36(5):854-857.
[10]REVERTE I,PUJOL A,DOMINGO J L,et al.Thyroid hormones and fear learning but not anxiety are affected in adult apoE transgenic mice exposed postnatally to decabromodiphenyl ether(BDE-209)[J].Physiol Behav,2014,133:81-91.
[11]KURIYAMA S N,WANNER A,FIDALGO-NETO A A,et al.Developmental exposure to low-dose PBDE-99:tissue distribution and thyroid hormone levels[J].Toxicology,2007,242(1/2/3):80-90.
[12]FOWLES J R,FAIRBROTHER A,BAECHER-STEPPAN L,et al.Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether(DE-71)in C57BL/6J mice[J].Toxicology,1994,86(1/2):49-61.
[13]ZHU B,WANG Q,WANG X,et al.Impact of co-exposure with lead and decabromodiphenyl ether(BDE-209)on thyroid function in zebrafish larvae[J].Aquat Toxicol,2014,157:186-195.
[14]HUANG F,WEN S,LI J,et al.The human body burden of polybrominated diphenyl ethers and their relationships with thyroid hormones in the general population in Northern China[J].Sci Total Environ,2014,466-467:609-615.
[15]SARKAR D,CHOWDHURY J P,SINGH S K.Effect of polybrominated diphenyl ether(BDE-209)on testicular steroidogenesis and spermatogenesis through altered thyroid status in adult mice[J].Gen Comp Endocrinol,2016,239:50-61.
[16]HAN Z,LI Y,ZHANG S,et al.Prenatal transfer of decabromodiphenyl ether(BDE-209)results in disruption of the thyroid system and developmental toxicity in zebrafish offspring[J].Aquat Toxicol,2017,190:46-52.
[17]张晓娜.久效磷对金鱼(Carassius auratus)甲状腺轴的干扰效应及作用机制研究[D].青岛:中国海洋大学,2014.
[18]蔡云梅,张文兵,盛国英,等.十溴联苯醚在单次暴露的孕和非孕SD大鼠血液内的吸收分布[J].生态环境学报,2010,19(5):1009-1013.
[19]季洁云,冯超,卢大胜,等.生物样品中多溴联苯醚及其代谢物检测方法的研究进展[J].环境与职业医学,2018,35(3):246-252.
[20]刘早玲,张建清.多溴联苯醚对甲状腺激素干扰毒性的研究进展[J].环境与职业医学,2010,27(2):107-112.
[21]HALLGREN S,SINJARI T,H?KANSSON H,et al.Effects of polybrominated diphenyl ethers(PBDEs)and polychlorinated biphenyls(PCBs)on thyroid hormone and vitamin A levels in rats and mice[J].Arch Toxicol,2001,75(4):200-208.
[22]李明圆,金军,杨从巧,等.生产源区人血中多溴联苯醚水平与甲状腺激素相关性研究[J].环境科学,2011,32(11):3271-3276.
[23]段晓梅,郝立月,李丽婷,等.高脂膳食诱导的甲状腺激素改变对肥胖易感性的影响[J].营养学报,2016,38(1):41-47.
[2]朱春艳,安月,钱波,等.三代小鼠十溴联苯醚灌胃染毒对子鼠(F1、F2)学习记忆能力的影响[J].环境与职业医学,2014,31(12):930-935.
[3]CHEN L,HUANG Y,XU Z,et al.Human exposure to PBDEs via house dust ingestion in Guangzhou,South China[J].Arch Environ Contam Toxicol,2011,60(3):556-564.
[4]AKUTSU K,TAKATORI S,NAKAZAWA H,et al.Dietary intake estimations of polybrominated diphenyl ethers(PBDEs)based on a total diet study in Osaka,Japan[J].Food Addit Contam Part B Surveill,2008,1(1):58-68.
[5]FOSTER W G,GREGOROVICH S,MORRISON K M,et al.Human maternal and umbilical cord blood concentrations of polybrominated diphenyl ethers[J].Chemosphere,2011,84(10):1301-1309.
[6]焦扬,邓琳,赵贺,等.北京市海淀区产妇母乳中多溴联苯醚的初步调查[J].环境与健康杂志,2013,30(4):328-331.
[7]张琳,田英,杨先丰,等.上海市某医院新生儿脐带血中多溴联苯醚水平及其对出生结局的影响[J].中华预防医学杂志,2011,45(6):490-493.
[8]ESKENAZI B,FENSTER L,CASTORINA R,et al.Acomparison of PBDE serum concentrations in Mexican and Mexican-American children living in California[J].Environ Health Perspect,2011,119(10):1442-1448.
[9]张洪梅,苏青,罗敏.甲状腺激素缺乏对不同发育时期大鼠脑组织氧化应激指标的影响[J].吉林大学学报(医学版),2010,36(5):854-857.
[10]REVERTE I,PUJOL A,DOMINGO J L,et al.Thyroid hormones and fear learning but not anxiety are affected in adult apoE transgenic mice exposed postnatally to decabromodiphenyl ether(BDE-209)[J].Physiol Behav,2014,133:81-91.
[11]KURIYAMA S N,WANNER A,FIDALGO-NETO A A,et al.Developmental exposure to low-dose PBDE-99:tissue distribution and thyroid hormone levels[J].Toxicology,2007,242(1/2/3):80-90.
[12]FOWLES J R,FAIRBROTHER A,BAECHER-STEPPAN L,et al.Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether(DE-71)in C57BL/6J mice[J].Toxicology,1994,86(1/2):49-61.
[13]ZHU B,WANG Q,WANG X,et al.Impact of co-exposure with lead and decabromodiphenyl ether(BDE-209)on thyroid function in zebrafish larvae[J].Aquat Toxicol,2014,157:186-195.
[14]HUANG F,WEN S,LI J,et al.The human body burden of polybrominated diphenyl ethers and their relationships with thyroid hormones in the general population in Northern China[J].Sci Total Environ,2014,466-467:609-615.
[15]SARKAR D,CHOWDHURY J P,SINGH S K.Effect of polybrominated diphenyl ether(BDE-209)on testicular steroidogenesis and spermatogenesis through altered thyroid status in adult mice[J].Gen Comp Endocrinol,2016,239:50-61.
[16]HAN Z,LI Y,ZHANG S,et al.Prenatal transfer of decabromodiphenyl ether(BDE-209)results in disruption of the thyroid system and developmental toxicity in zebrafish offspring[J].Aquat Toxicol,2017,190:46-52.
[17]张晓娜.久效磷对金鱼(Carassius auratus)甲状腺轴的干扰效应及作用机制研究[D].青岛:中国海洋大学,2014.
[18]蔡云梅,张文兵,盛国英,等.十溴联苯醚在单次暴露的孕和非孕SD大鼠血液内的吸收分布[J].生态环境学报,2010,19(5):1009-1013.
[19]季洁云,冯超,卢大胜,等.生物样品中多溴联苯醚及其代谢物检测方法的研究进展[J].环境与职业医学,2018,35(3):246-252.
[20]刘早玲,张建清.多溴联苯醚对甲状腺激素干扰毒性的研究进展[J].环境与职业医学,2010,27(2):107-112.
[21]HALLGREN S,SINJARI T,H?KANSSON H,et al.Effects of polybrominated diphenyl ethers(PBDEs)and polychlorinated biphenyls(PCBs)on thyroid hormone and vitamin A levels in rats and mice[J].Arch Toxicol,2001,75(4):200-208.
[22]李明圆,金军,杨从巧,等.生产源区人血中多溴联苯醚水平与甲状腺激素相关性研究[J].环境科学,2011,32(11):3271-3276.
[23]段晓梅,郝立月,李丽婷,等.高脂膳食诱导的甲状腺激素改变对肥胖易感性的影响[J].营养学报,2016,38(1):41-47.