邻苯二甲酸酯及Wnt通路影响配子及胚胎发育的研究进展
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摘要
邻苯二甲酸酯(PAEs)作为添加剂被广泛应用于食品、建材、医疗等各行各业中。由于PAEs难以形成强力的共价键,PAEs会不断泄露到环境中并通过人们的饮食、日常生活用品接触等在人体中蓄积。作为环境内分泌干扰物中的一大类,PAEs会造成影响深远的生殖内分泌干扰效应,对配子及胚胎发育产生影响。而Wnt家族基因及其产物可通过多环节、多作用位点影响基因表达或促进细胞增殖,从而诱导组织分化来调控生长发育。综述PAEs的生化性质和污染途径以及PAEs的内分泌干扰机制,并综述Wnt及其他可能介导PAEs对配子及胚胎发育造成影响的信号通路或机制。
Phthalates(PAEs) are widely used as additives in food, building materials, medical and other industries. Because PAEs are difficult to form strong covalent bonds, they will continue to leak into the environment and be absorbed during people's daily life. As a large class of environmental endocrine disruptors that disrupt reproductive endocrine, PAEs affect gametes and embryo development strongly. The factors of Wnt family participate in the regulation of tissue differentiation, growth and development via multiple mechanisms such as affecting gene expression and inducing cell proliferation. This paper reviews the biochemical character, endocrine disruption mechanisms and pollution conditions of PAEs, and the related Wnt signaling pathways that may affect gametes and embryo development.
Phthalates(PAEs) are widely used as additives in food, building materials, medical and other industries. Because PAEs are difficult to form strong covalent bonds, they will continue to leak into the environment and be absorbed during people's daily life. As a large class of environmental endocrine disruptors that disrupt reproductive endocrine, PAEs affect gametes and embryo development strongly. The factors of Wnt family participate in the regulation of tissue differentiation, growth and development via multiple mechanisms such as affecting gene expression and inducing cell proliferation. This paper reviews the biochemical character, endocrine disruption mechanisms and pollution conditions of PAEs, and the related Wnt signaling pathways that may affect gametes and embryo development.
引文
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[25]Li N,Li S,Wang Y,et al.Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/β-catenin signaling pathway[J].Cell Biol Int,2017,41(8):898-907.
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[27]Qiao GY,Dong BW,Zhu CJ,et al.Deregulation of WNT2/FZD3/β-catenin pathway compromises the estrogen synthesis in cumulus cells from patients with polycystic ovary syndrome[J].Biochem Biophys Res Commun,2017,493(1):847-854.
[28]Katz TA,Yang Q,Trevio LS,et al.Endocrine-disrupting chemicals and uterine fibroids[J].Fertil Steril,2016,106(4):967-977.
[29]Veltri A,Lang C,Lien WH.Concise Review:Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells[J].Stem Cells,2018,36(1):22-35.
[30]Zhang LF,Qin C,Wei YF,et al.Differential expression of the Wnt/β-catenin pathway in the genital tubercle(GT)of fetal male rat following maternal exposure to di-n-butyl phthalate(DBP)[J].Syst Biol Reprod Med,2011,57(5):244-250.
[31]UstündagUV,Unal I,AtePS,et al.Bisphenol A and di(2-ethylhexyl)phthalate exert divergent effects on apoptosis and the Wnt/β-catenin pathway in zebrafish embryos:A possible mechanism of endocrine disrupting chemical action[J].Toxicol Ind Health,2017,33(12):901-910.
[2]Sun Y,Huang H,Sun Y,et al.Occurrence of estrogenic endocrine disrupting chemicals concern in sewage plant effluent[J].Front Environ Sci Eng,2014,8(1):18-26.
[3]Futran Fuhrman V,Tal A,Arnon S.Why endocrine disrupting chemicals(EDCs)challenge traditional risk assessment and how to respond[J].J Hazard Mater,2015,286:589-611.
[4]曹龙,张朝升,陈秋丽,等.邻苯二甲酸酯的环境污染和生态行为及毒理效应研究进展[J].生态毒理学报,2018,13(2):34-46.
[5]Zhou L,Lei Y,Zhang D,et al.An ultra-sensitive monoclonal antibody-based enzyme-linked immunosobent assay for dibutyl phthalate in human urinary[J].Sci Total Environ,2016,541:570-578.
[6]Machtinger R,Gaskins AJ,Racowsky C,et al.Urinary concentrations of biomarkers of phthalates and phthalate alternatives and IVF outcomes[J].Environ Int,2018,111:23-31.
[7]王晓阳,戴家银,张红霞.邻苯二甲酸丁基苄酯的雄性生殖和发育毒性研究[J].中国科学:生命科学,2016,46(1):113-119.
[8]Grossman D,Kalo D,Gendelman M,et al.Effect of di-(2-ethylhexyl)phthalate and mono-(2-ethylhexyl)phthalate on in vitro developmental competence of bovine oocytes[J].Cell Biol Toxicol,2012,28(6):383-396.
[9]Hannon PR,Brannick KE,Wang W,et al.Di(2-ethylhexyl)phthalate inhibits antral follicle growth,induces atresia,and inhibits steroid hormone production in cultured mouse antral follicles[J].Toxicol Appl Pharmacol,2015,284(1):42-53.
[10]Mínguez-Alarcón L,Souter I,Chiu YH,et al.Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester,a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate(DINCH),and markers of ovarian response among women attending a fertility center[J].Environ Res,2016,151:595-600.
[11]Karwacka A,Zamkowska D,Radwan M,et al.Exposure to modern,widespread environmental endocrine disrupting chemicals and their effect on the reproductive potential of women:an overview of current epidemiological evidence[J].Hum Fertil(Camb),2019,22(1):2-25.
[12]Pocar P,Fiandanese N,Berrini A,et al.Maternal exposure to di(2-ethylhexyl)phthalate(DEHP)promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice[J].Toxicol Appl Pharmacol,2017,322:113-121.
[13]Hauser R,Gaskins AJ,Souter I,et al.Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization:Results from the EARTH Study[J].Environ Health Perspect,2016,124:831-839.
[14]Ahmad R,Gautam AK,Verma Y,et al.Effects of in utero di-butyl phthalate and butyl benzyl phthalate exposure on offspring development and male reproduction of rat[J].Environ Sci Pollut Res Int,2014,21(4):3156-3165.
[15]Ma YB,Jia PP,Junaid M,et al.Reproductive effects linked to DNA methylation in male zebrafish chronically exposed to environmentally relevant concentrations of di-(2-ethylhexyl)phthalate[J].Environ Pollut,2018,237:1050-1061.
[16]Gao HT,Xu R,Cao WX,et al.Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats[J].Food Chem Toxicol,2017,101:94-104.
[17]Wu H,Ashcraft L,Whitcomb BW,et al.Parental contributions to early embryo development:influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment[J].Hum Reprod,2017,32(1):65-75.
[18]Chen X,Xu S,Tan T,et al.Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures[J].Int J Environ Res Public Health,2014,11(3):3156-3168.
[19]穆希岩,李成龙,黄瑛,等.两种邻苯二甲酸酯类污染物对斑马鱼胚胎发育的影响[J].中国环境科学,2017,37(9):3566-3575.
[20]Zhong J,Baccarelli AA,Mansur A,et al.Maternal Phthalate and Personal Care Products Exposure Alters Extracellular Placental miRNA Profile in Twin Pregnancies[J].Reprod Sci,2019,26(2):289-294.
[21]Tepekoy F,Akkoyunlu G,Demir R.The role of Wnt signaling members in the uterus and embryo during pre-implantation and implantation[J].J Assist Reprod Genet,2015,32(3):337-346.
[22]Nusse R,Clevers H.Wnt/β-Catenin Signaling,Disease,and Emerging Therapeutic Modalities[J].Cell,2017,169(6):985-999.
[23]Sonderegger S,Pollheimer J,Kn觟fler M.Wnt signalling in implantation,decidualisation and placental differentiation--review[J].Placenta,2010,31(10):839-847.
[24]Zhang Q,Yan J.Update of Wnt signaling in implantation and decidualization[J].Reprod Med Biol,2015,15(2):95-105.
[25]Li N,Li S,Wang Y,et al.Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/β-catenin signaling pathway[J].Cell Biol Int,2017,41(8):898-907.
[26]Fairbairn EA,Bonthius J,Cherr GN.Polycyclic aromatic hydrocarbons and dibutyl phthalate disrupt dorsal-ventral axis determination via the Wnt/β-catenin signaling pathway in zebrafish embryos[J].Aquat Toxicol,2012,124-125:188-196.
[27]Qiao GY,Dong BW,Zhu CJ,et al.Deregulation of WNT2/FZD3/β-catenin pathway compromises the estrogen synthesis in cumulus cells from patients with polycystic ovary syndrome[J].Biochem Biophys Res Commun,2017,493(1):847-854.
[28]Katz TA,Yang Q,Trevio LS,et al.Endocrine-disrupting chemicals and uterine fibroids[J].Fertil Steril,2016,106(4):967-977.
[29]Veltri A,Lang C,Lien WH.Concise Review:Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells[J].Stem Cells,2018,36(1):22-35.
[30]Zhang LF,Qin C,Wei YF,et al.Differential expression of the Wnt/β-catenin pathway in the genital tubercle(GT)of fetal male rat following maternal exposure to di-n-butyl phthalate(DBP)[J].Syst Biol Reprod Med,2011,57(5):244-250.
[31]UstündagUV,Unal I,AtePS,et al.Bisphenol A and di(2-ethylhexyl)phthalate exert divergent effects on apoptosis and the Wnt/β-catenin pathway in zebrafish embryos:A possible mechanism of endocrine disrupting chemical action[J].Toxicol Ind Health,2017,33(12):901-910.