TCDD诱导胎鼠腭裂的实验研究进展
|
摘要
目的:总结归纳2,3,7,8-四氯二苯二英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)诱导胎鼠腭裂的实验研究现状,为深入探讨TCDD致胎鼠腭裂的发生机制提供新的思路。方法:通过中国知网、NCBI等国内外文献库检索"TCDD""腭裂"等关键词,搜集已有文献资料。结果:目前的资料显示,可以通过约20μg/kg剂量的TCDD给予孕第9~14天的小鼠单次灌胃建立稳定的胎鼠腭裂模型。在此基础上发现,TCDD诱导不涉及腭突体积变化,主要通过抑制腭突接触融合而发挥致腭裂效应。对于发育中的腭组织细胞,TCDD能改变一系列调节细胞增殖、分化、凋亡的生长因子及其受体的表达,主要包括表皮细胞生长因子(epidermal growth factor,EGF)、转化生长因子(transforming growth factor,TGF)、芳香烃受体(aryl hydrocarbon receptor,AhR)。这些分子的表达变化尚存在争议。腭融合过程中发挥关键作用的腭中缝上皮细胞(medial edge epithelium,MEE),其细胞命运转归尚未阐明。结论:TCDD诱导胎鼠腭裂的体内实验基础相对完善。腭发育调控机制纷繁复杂,注重器官发育的时空动态性对于进一步研究至关重要。腭器官离体培养将是重要的体外实验环节。实验技术和条件的变革对于本领域的研究进展显得愈加迫切。
Objective:To summarize the experimental research progress on murine cleft palate induced by 2,3,7,8-tetrachlorodibenzop-dioxin(TCDD) and to provide new thoughts for further mechanisms in TCDD-induced murine cleft palate.Methods:Literatures from domestic and foreign database including CNKI and NCBI were reviewed,searching the keywords of "cleft palate""TCDD",etc.Results:Data up till now showed that a stable fetal cleft palate model could be established by treating pregnant mice with a single oral administration of approximate 20 μg/kg of TCDD from gestation day 9 to 14.Palate size altering was not involved in this model.TCDD inhibited palate contact and fusion to induce fetal cleft palate.TCDD altered the expression of a series of growth factors and receptors including epidermal growth factor(EGF),transforming growth factor(TGF) and aryl hydrocarbon receptor(Ah R) which could regulate cell proliferation,differentiation and apoptosis in palate tissue.Expression alterations of these molecules were still controversial.The cell fate of medial edge epithelium(MEE)which was vital to palate fusion was still not clear.Conclusion:The basis of studies in vivo on TCDD-induced fetal cleft palate is comparatively refined.Regulation mechanisms in palatal devel opment are complicated.It is crucial to notice the space-time dynamics in organgenesis in further research.Culture of palate organ will be an important part of studies in vitro.Revolution of experimental technique and condition appears even more necessary and urgent for research progress in this field.
Objective:To summarize the experimental research progress on murine cleft palate induced by 2,3,7,8-tetrachlorodibenzop-dioxin(TCDD) and to provide new thoughts for further mechanisms in TCDD-induced murine cleft palate.Methods:Literatures from domestic and foreign database including CNKI and NCBI were reviewed,searching the keywords of "cleft palate""TCDD",etc.Results:Data up till now showed that a stable fetal cleft palate model could be established by treating pregnant mice with a single oral administration of approximate 20 μg/kg of TCDD from gestation day 9 to 14.Palate size altering was not involved in this model.TCDD inhibited palate contact and fusion to induce fetal cleft palate.TCDD altered the expression of a series of growth factors and receptors including epidermal growth factor(EGF),transforming growth factor(TGF) and aryl hydrocarbon receptor(Ah R) which could regulate cell proliferation,differentiation and apoptosis in palate tissue.Expression alterations of these molecules were still controversial.The cell fate of medial edge epithelium(MEE)which was vital to palate fusion was still not clear.Conclusion:The basis of studies in vivo on TCDD-induced fetal cleft palate is comparatively refined.Regulation mechanisms in palatal devel opment are complicated.It is crucial to notice the space-time dynamics in organgenesis in further research.Culture of palate organ will be an important part of studies in vitro.Revolution of experimental technique and condition appears even more necessary and urgent for research progress in this field.
引文
[1]Li CH,Shi B,He W,et al.Is it possible to antagonize 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate by prenatal administration of folic acid?An experimental study[J].Toxicol Ind Health,2010,26(5):281-286.
[2]Abbott BD,Harris MW,Birnbaum LS.Comparisons of the effects of TCDD and hydrocortisone on growth factor expression provide insight into their interaction in the embryonic mouse palate[J].Teratology,1992,45(1):35-53.
[3]Abbott BD,Birnbaum LS.Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD[J].Toxicol Appl Pharmacol,1989,99(2):287-301.
[4]Furukawa S,Usuda K,Abe M,et al.Histopathological findings of cleft palate in rat embryos induced by triamcinolone acetonide[J].J Vet Med Sci,2004,66(4):397-402.
[5]Bittencourt MA,Bolognese AM.Epithelial alterations of secondary palate formation[J].Braz Dent J,2000,11(2):117-126.
[6]Abbott BD,Harris MW,Birnbaum LS.Etiology of retinoic acid-induced cleft palate varies with the embryonic stage[J].Teratology,1989,40(6):533-553.
[7]Cuervo R,Valencia C,Chandraratna RA,et al.Programmed cell death is required for palate shelf fusion and is regulated by retinoic acid[J].Dev Biol,2002,245(1):145-156.
[8]Thomae TL,Stevens EA,Bradfield CA.Transforming growth factorbeta3 restores fusion in palatal shelves exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J].J Biol Chem,2005,280(13):12742-12746.
[9]Fujiwara K,Yamada T,Mishima K,et al.Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice[J].Congenit Anom(Kyoto),2008,48(2):68-73.
[10]Pratt RM.Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate[J].Environ Health Perspect,1985,61:35-40.
[11]Abbott BD,Birnbaum LS.Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves[J].Teratology,1990,42(6):597-610.
[12]Abbott BD,Pratt RM.Retinoic acid alters epithelial differentiation during palatogenesis[J].J Craniofac Genet Dev Biol,1991,11(4):315-325.
[13]Abbott BD,Birnbaum LS.TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD[J].Toxicol Appl Pharmacol,1990,106(3):418-432.
[14]Naitoh H,Mori C,Nishimura Y,et al.Altered expression of retinoic acid(RA)receptor m RNAs in the fetal mouse secondary palate by all-trans and 13-cis RAs:implications for RA-induced teratogenesis[J].J Craniofac Genet Dev Biol,1998,18(4):202-210.
[15]Nugent P,Sucov HM,Pisano MM,et al.The role of RXR-alpha in retinoic acid-induced cleft palate as assessed with the RXR-alpha knockout mouse[J].Int J Dev Biol,1999,43(6):567-570.
[16]Abbott BD,Perdew GH,Buckalew AR,et al.Interactive regulation of Ah and glucocorticoid receptors in the synergistic induction of cleft palate by 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone[J].Toxicol Appl Pharmacol,1994,128(1):138-150.
[17]Jacobs H,Dennefeld C,Feret B,et al.Retinoic acid drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development[J].Environ Health Perspect,2011,119(11):1590-1595.
[18]Bryant PL,Schmid JE,Fenton SE,et al.Teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in mice lacking the expression of EGF and/or TGF-alpha[J].Toxicol Sci,2001,62(1):103-114.
[19]Abbott BD,Buckalew AR,De Vito MJ,et al.EGF and TGF-alpha expression influence the developmental toxicity of TCDD:dose response and Ah R phenotype in EGF,TGF-alpha,and EGF+TGF-alpha knockout mice[J].Toxicol Sci,2003,71(1):84-95.
[20]Gan LQ,Fu YX,Liu X,et al.Transforming growth factor-beta3expression up-regulates on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice[J].Toxicol Ind Health,2009,25(7):473-478.
[21]Lamb JC 4th,Harris MW,Mc Kinney JD,et al.Effects of thyroid hormones on the induction of cleft palate by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in C57BL/6N mice[J].Toxicol Appl Pharmacol,1986,84(1):115-124.
[22]Jang JY,Shin S,Choi BI,et al.Antiteratogenic effects of alphanaphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)exposed mice in utero[J].Reprod Toxicol,2007,24(3-4):303-309.
[23]Jang JY,Park D,Shin S,et al.Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J].Eur J Pharmacol,2008,591(1-3):280-283.
[24]Shiota K,Kosazuma T,Klug S,et al.Development of the fetal mouse palate in suspension organ culture[J].Acta Anat,1990,137(1):59-64.
[25]王晨,袁心刚,傅跃先,等.TCDD诱导的胎鼠腭发育过程中DNA甲基化变化[J].中华整形外科杂志,2016,32(5):362-367.
[26]刘翠苹,袁心刚,傅跃先,等.组蛋白H3乙酰化在TCDD致胎鼠腭裂发生中的作用[J].中华整形外科杂志,2014,30(5):369-373.
[2]Abbott BD,Harris MW,Birnbaum LS.Comparisons of the effects of TCDD and hydrocortisone on growth factor expression provide insight into their interaction in the embryonic mouse palate[J].Teratology,1992,45(1):35-53.
[3]Abbott BD,Birnbaum LS.Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD[J].Toxicol Appl Pharmacol,1989,99(2):287-301.
[4]Furukawa S,Usuda K,Abe M,et al.Histopathological findings of cleft palate in rat embryos induced by triamcinolone acetonide[J].J Vet Med Sci,2004,66(4):397-402.
[5]Bittencourt MA,Bolognese AM.Epithelial alterations of secondary palate formation[J].Braz Dent J,2000,11(2):117-126.
[6]Abbott BD,Harris MW,Birnbaum LS.Etiology of retinoic acid-induced cleft palate varies with the embryonic stage[J].Teratology,1989,40(6):533-553.
[7]Cuervo R,Valencia C,Chandraratna RA,et al.Programmed cell death is required for palate shelf fusion and is regulated by retinoic acid[J].Dev Biol,2002,245(1):145-156.
[8]Thomae TL,Stevens EA,Bradfield CA.Transforming growth factorbeta3 restores fusion in palatal shelves exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J].J Biol Chem,2005,280(13):12742-12746.
[9]Fujiwara K,Yamada T,Mishima K,et al.Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice[J].Congenit Anom(Kyoto),2008,48(2):68-73.
[10]Pratt RM.Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate[J].Environ Health Perspect,1985,61:35-40.
[11]Abbott BD,Birnbaum LS.Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves[J].Teratology,1990,42(6):597-610.
[12]Abbott BD,Pratt RM.Retinoic acid alters epithelial differentiation during palatogenesis[J].J Craniofac Genet Dev Biol,1991,11(4):315-325.
[13]Abbott BD,Birnbaum LS.TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD[J].Toxicol Appl Pharmacol,1990,106(3):418-432.
[14]Naitoh H,Mori C,Nishimura Y,et al.Altered expression of retinoic acid(RA)receptor m RNAs in the fetal mouse secondary palate by all-trans and 13-cis RAs:implications for RA-induced teratogenesis[J].J Craniofac Genet Dev Biol,1998,18(4):202-210.
[15]Nugent P,Sucov HM,Pisano MM,et al.The role of RXR-alpha in retinoic acid-induced cleft palate as assessed with the RXR-alpha knockout mouse[J].Int J Dev Biol,1999,43(6):567-570.
[16]Abbott BD,Perdew GH,Buckalew AR,et al.Interactive regulation of Ah and glucocorticoid receptors in the synergistic induction of cleft palate by 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone[J].Toxicol Appl Pharmacol,1994,128(1):138-150.
[17]Jacobs H,Dennefeld C,Feret B,et al.Retinoic acid drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development[J].Environ Health Perspect,2011,119(11):1590-1595.
[18]Bryant PL,Schmid JE,Fenton SE,et al.Teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in mice lacking the expression of EGF and/or TGF-alpha[J].Toxicol Sci,2001,62(1):103-114.
[19]Abbott BD,Buckalew AR,De Vito MJ,et al.EGF and TGF-alpha expression influence the developmental toxicity of TCDD:dose response and Ah R phenotype in EGF,TGF-alpha,and EGF+TGF-alpha knockout mice[J].Toxicol Sci,2003,71(1):84-95.
[20]Gan LQ,Fu YX,Liu X,et al.Transforming growth factor-beta3expression up-regulates on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice[J].Toxicol Ind Health,2009,25(7):473-478.
[21]Lamb JC 4th,Harris MW,Mc Kinney JD,et al.Effects of thyroid hormones on the induction of cleft palate by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in C57BL/6N mice[J].Toxicol Appl Pharmacol,1986,84(1):115-124.
[22]Jang JY,Shin S,Choi BI,et al.Antiteratogenic effects of alphanaphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)exposed mice in utero[J].Reprod Toxicol,2007,24(3-4):303-309.
[23]Jang JY,Park D,Shin S,et al.Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J].Eur J Pharmacol,2008,591(1-3):280-283.
[24]Shiota K,Kosazuma T,Klug S,et al.Development of the fetal mouse palate in suspension organ culture[J].Acta Anat,1990,137(1):59-64.
[25]王晨,袁心刚,傅跃先,等.TCDD诱导的胎鼠腭发育过程中DNA甲基化变化[J].中华整形外科杂志,2016,32(5):362-367.
[26]刘翠苹,袁心刚,傅跃先,等.组蛋白H3乙酰化在TCDD致胎鼠腭裂发生中的作用[J].中华整形外科杂志,2014,30(5):369-373.