环境内分泌干扰物的女性生殖毒性及其在妇科肿瘤发生发展中的作用
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摘要
环境内分泌干扰物是一类广泛存在于环境中,进入机体后可以干扰机体内分泌系统和天然激素的功能,进而导致器官损害和疾病发生的外源性物质或混合物。近年来,乳腺癌、卵巢癌、子宫内膜癌等女性雌激素依赖性肿瘤发病率逐年增加。研究表明,环境内分泌干扰物对女性生殖系统具有毒性作用,且环境内分泌干扰物的暴露可以增加激素敏感性器官的肿瘤发生率。本文就环境内分泌干扰物中具有代表性的三类物质邻苯二甲酸酯(PAEs)、多氯联苯(PCBs)和双酚A(BPA)对生殖系统的影响及其在妇科肿瘤发生发展中的作用进行综述,以期为预防妇科肿瘤、环境内分泌干扰物的毒作用研究及污染防控提供依据。
Environmental endocrine disruptors(EEDs) refer to a class of exogenous substances or their mixtures widely present in environment that are known to interfere with human endocrine system and the function of natural hormones, leading to organ/tissue damage and diseases. In recent years, there are evident increasing incidences of female estrogen-dependent tumors such as breast cancer, ovarian cancer, and endometrial cancer. A great number of studies indicate that exposure to EEDs is toxic to female reproductive system and one of the underlying etiological factors for developing tumors in hormone-sensitive organs. This paper systematically reviewed phthalates(PAEs), polychlorinated biphenyls(PCBs), and bisphenol A(BPA) about their effects on female reproductive system and their implications in developing gynecological tumors, aiming to provide evidence for further studying gynecological tumor prevention, EEDs toxicity, and pollution prevention and control.
Environmental endocrine disruptors(EEDs) refer to a class of exogenous substances or their mixtures widely present in environment that are known to interfere with human endocrine system and the function of natural hormones, leading to organ/tissue damage and diseases. In recent years, there are evident increasing incidences of female estrogen-dependent tumors such as breast cancer, ovarian cancer, and endometrial cancer. A great number of studies indicate that exposure to EEDs is toxic to female reproductive system and one of the underlying etiological factors for developing tumors in hormone-sensitive organs. This paper systematically reviewed phthalates(PAEs), polychlorinated biphenyls(PCBs), and bisphenol A(BPA) about their effects on female reproductive system and their implications in developing gynecological tumors, aiming to provide evidence for further studying gynecological tumor prevention, EEDs toxicity, and pollution prevention and control.
引文
[1]BERGMAN A,HEINDEL J J,KASTEN T,et al.The impact of endocrine disruption:a consensus statement on the state of the science[J].Environ Health Perspect,2013,121(4):A104-A106.
[2]LEGLER J,FLETCHER T,GOVARTS E,et al.Obesity,diabetes,and associated costs of exposure to endocrinedisrupting chemicals in the European Union[J].J Clin Endocrinol Metab,2015,100(4):1278-1288.
[3]NOHYNEK G J,BORGERT C J,DIETRICH D,et al.Endocrine disruption:fact or urban legend?[J].Toxicol Lett,2013,223(3):295-305.
[4]BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CACancer J Clin,2018,68(6):394-424.
[5]FERNANDEZ S V,HUANG Y,SNIDER K E,et al.Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure[J].Int J Oncol,2012,41(1):369-377.
[6]LANG PODRATZ P,DELGADO FILHO V S,LOPES P F,et al.Tributyltin impairs the reproductive cycle in female rats[J].J Toxicol Environ Health A,2012,75(16-17):1035-1046.
[7]FUCIC A,GAMULIN M,FERENCIC Z,et al.Environmental exposure to xenoestrogens and oestrogen related cancers:reproductive system,breast,lung,kidney,pancreas,and brain[J].Environ Health,2012,11(s1):s8.
[8]BERGéA,CLADIèRE M,GASPERI J,et al.Meta-analysis of environmental contamination by phthalates[J].Environ Sci Pollut Res,2013,20(11):8057-8076.
[9]FU Z,ZHAO F,CHEN K et al.Association between urinary phthalate metabolites and risk of breast cancer and uterine leiomyoma[J].Reprod Toxicol,2017,74:134-142.
[10]LEE H S,PARK E J,OH J H,et al.Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAPkinase activity[J].Biosci Biotechnol Biochem,2014,78(8):1371-1375.
[11]POIDATZ D,DOS SANTOS E,BRULéA,et al.Estrogenrelated receptor gamma modulates energy metabolism target genes in human trophoblast[J].Placenta,2012,33(9):688-695.
[12]RITTER R,SCHERINGER M,MACLEOD M,et al.Intrinsic human elimination half-lives of polychlorinated biphenyls derived from the temporal evolution of cross-sectional biomonitoring data from the United Kingdom[J].Environ Health Perspect,2011,119(2):225-231.
[13]KEZIOS K L,LIU X,CIRILLIO P M,et al.Prenatal polychlorinated biphenyl exposure is associated with decreased gestational length but not birth weight:archived samples from the Child Health and Development Studies pregnancy cohort[J].Environ Health,2012,11:49.
[14]XU C,CHEN JA,QIU Z,et al.Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl)phthalate[J].Toxicol Lett,2010,199(3):323-332.
[15]BONILLA E,DEL MAZO J,et al.Deregulation of the Sod1and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl)phthalate(MEHP)[J].Reprod Toxicol,2010,30(3):387-392.
[16]ZHANG T,LI L,QIN X S,et al.Di-(2-ethylhexyl)phthalate and bisphenol A exposure impairs mouse primordial follicle assembly in vitro[J].Environ Mol Mutagen,2014,55(4):343-353.
[17]LIU J,WANG W,ZHU J,et al.Di(2-ethylhexyl)phthalate(DEHP)influences follicular development in mice between the weaning period and maturity by interfering with ovarian development factors and microRNAs[J].Environ Toxicol,2018,33(5):535-544.
[18]MUCZYNSKI V,LECUREUIL C,MESSIAEN S,et al.Cellular and molecular effect of MEHP involving LXRαin Human Fetal testis and ovary[J].PLoS One,2012,7(10):e48266.
[19]MURATI T,?IMI?B,BROZOVIC A,et al.PCB 77 action in ovary cells-toxic effects,apoptosis induction and cell cycle analysis[J].Toxicol Mech Methods,2015,25(4):302-311.
[20]YANG Q,ZHAO Y,QIU X,et al.Association of serum levels of typical organic pollutants with polycystic ovary syndrome(PCOS):a case-control study[J].Hum Reprod,2015,30(8):1964-1973.
[21]VAGI S J,AZZIZ-BAUMGARTNER E,SJ?DIN A,et al.Exploring the potential association between brominated diphenyl ethers,polychlorinated biphenyls,organochlorine pesticides,perfluorinated compounds,phthalates,and bisphenol a in polycystic ovary syndrome:a case-control study[J].BMC Endocr Disord,2014,14:86.
[22]KANDARAKI E,CHATZIGEORGIOU A,LIVADAS S,et al.Endocrine disruptors and polycystic ovary syndrome(PCOS):elevated serum levels of bisphenol A in women with PCOS[J].J Clin Endocrinol Metab,2011,96(3):E480-E484.
[23]GORE A C,CHAPPELL V A,FENTON S E,et al.EDC-2:the endocrine society's second scientific statement on endocrine-disrupting chemicals[J].Endocr Rev,2015,36(6):E1-E150.
[24]KIM S H,CHO S,IHM H J.Possible role of phthalate in the pathogenesis of endometriosis:In vitro,animal,and human data[J].J Clin Endocrinol Metab,2015,100(12):E1502-1511.
[25]KIM J H,KIM S H,OH Y S,et al.In vitro effects of phthalate esters in human myometrial and leiomyoma cells and increased urinary level of phthalate metabolite in women with uterine leiomyoma[J].Fertil Steril,2017,107(4):1061-1069.e1.
[26]CRAIN D A,JANSSEN S J,EDWARDS T M,et al.Female reproductive disorders:the roles of endocrine-disrupting compounds and developmental timing[J].Fertil Steril,2008,90(4):911-940.
[27]POLLACK A Z,BUCK LOUIS G M,CHEN Z,et al.Bisphenol A,benzophenone-type ultraviolet filters,and phthalates in relation to uterine leiomyoma[J].Environ Res,2015,137:101-107.
[28]ISHIHARA H,YAMASHITA S,FUJII S,et al.DNA methylation marker to estimate the breast cancer cell fraction in DNAsamples[J].Med Oncol,2018,35(11):147.
[29]KANG C,LEROITH D,GALLAGHER E J.Diabetes,obesity,and breast cancer[J].Endocrinology,2018,159(11):3801-3812.
[30]CORMANIQUE T F,ALMEIDA L E,RECH C A,et al.Chronic psychological stress and its impact on the development of aggressive breast cancer[J].Einstein(S?o Paulo),2015,13(3):352-356.
[31]SHRIDHAR K,SINGH G,DEY S,et al.Dietary patterns and breast cancer risk:a multi-centre case control study among north indian women[J].Int J Environ Res Public Health,2018,15(9):1946.
[32]SIFAKIS S,ANDROUTSOPOULOS V P,TSATSAKIS A M,et al.Human exposure to endocrine disrupting chemicals:effects on the male and female reproductive systems[J].Environ Toxicol Pharmacol,2017,51:56-70.
[33]HALL J M,KORACH K S.Endocrine disrupting chemicals promote the growth of ovarian cancer cells via the ER-CXCL12-CXCR4 signaling axis[J].Mol Carcinog,2013,52(9):715-725.
[34]CHEN F P,CHIEN M H,CHERN I Y.Impact of low concentrations of phthalates on the effects of 17β-estradiol in MCF-7 breast cancer cells[J].Taiwan J Obstet Gynecol,2016,55(6):826-834.
[35]LIU S,LI S,DU Y.Polychlorinated biphenyls(PCBs)enhance metastatic properties of breast cancer cells by activating rhoassociated kinase(ROCK)[J].PLoS One,2010,5(6):e11272.
[36]SOTO A M,BRISKEN C,SCHAEBERLE C,et al.Does cancer start in the womb?Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors[J].J Mammary Gland Biol Neoplasia,2013,18(2):199-208.
[37]HOLMES A K,KOLLER K R,KIESZAK S M,et al.Casecontrol study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women[J].Int J Circumpolar Health,2014,73:25760.
[38]PARADA H J R,GAMMON M D,CHEN J,et al.Urinary phthalate metabolite concentrations and breast cancer incidence and survival following breast cancer:the long island breast cancer study project[J].Environ Health Perspect,2018,126(4):047013.
[39]SPRAGUE B L,TRENTHAM-DIETZ A,HEDMAN C J,et al.Circulating serum xenoestrogens and mammographic breast density[J].Breast Cancer Res,2013,15(3):R45
[40]DONAT-VARGAS C,?KESSON A,BERGLUND M,et al.Dietary exposure to polychlorinated biphenyls and risk of breast,endometrial and ovarian cancer in a prospective cohort[J].Br J Cancer,2016,115(9):1113-1121.
[41]WIELS?E M,KERN P,BONEFELD-J?RGENSEN EC.Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit:a case control study[J].Environ Health,2017,16(1):56.
[42]YANG O,KIM L H,WEON J I,et al.Endocrine-disrupting chemicals:review of toxicological mechanisms using molecular pathway analysis[J].J Cancer Prev,2015,20(1):12-24.
[43]NEWBOLD R R,JEFFERSON W N,PADILLA-BANKS E.Longterm adverse effects of neonatal exposure to bisphenol a on the murine female reproductive tract[J].Reprod Toxicol,2007,24(2):253-258.
[44]KIM Y S,HWANG K A,HYUN S H,et al.Bisphenol A and nonylphenol have the potential to stimulate the migration of ovarian cancer cells by inducing epithelial-mesenchymal transition via an estrogen receptor dependent pathway[J].Chem Res Toxicol,2015,28(4):662-671.
[45]YONEOKA Y,YOSHIDA H,ISHIKAWA M,et al.Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma[J].J Gynecol Oncol,2019,30:e7.
[46]LI R,YU C,GAO R,et al.Effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice[J].JHazard Mater,2012,241-242:231-240.
[47]CHEN Y,HUANG Q,CHEN Q,et al.The inflammation and estrogen metabolism impacts of polychlorinated biphenyls on endometrial cancer cells[J].Toxicol in Vitro,2015,29(2):308-313.
[48]HELMESTAM M,DAVEY E,STAVREUS-EVERS A,et al.Bisphenol A affects human endometrial endothelial cell angiogenic activity in vitro[J].Reprod Toxicol,2014,46:69-76.
[49]BROMER J G,ZHOU Y,TAYLOR M B,et al.Bisphenol-Aexposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response[J].FASEB J,2010,24(7):2273-2280
[50]REICH O,REGAUER S,SCHARF S.High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma--report of two cases[J].Eur J Gynaecol Oncol,2010,31(1):105-106.
[51]PARK M A,HWANG K A,LEE H R,et al.Cell growth of BG-1ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin Dand cyclin-dependent kinase-4 genes[J].Mol Med Rep,2012,5(3):761-766.
[52]EL-HEFNAWY T,HERNANDEZ C,STABILE L P.The endocrine disrupting alkylphenols and 4,4'-DDT interfere with estrogen conversion and clearance by mouse liver cytosol[J].Reprod Biol,2017,17(3):185-192.
[53]WANG W,CRAIG Z R,BASAVARAJAPPA M S,et al.Mono-(2-ethylhexyl)phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles[J].Biol Reprod,2012,87(6):152.
[2]LEGLER J,FLETCHER T,GOVARTS E,et al.Obesity,diabetes,and associated costs of exposure to endocrinedisrupting chemicals in the European Union[J].J Clin Endocrinol Metab,2015,100(4):1278-1288.
[3]NOHYNEK G J,BORGERT C J,DIETRICH D,et al.Endocrine disruption:fact or urban legend?[J].Toxicol Lett,2013,223(3):295-305.
[4]BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CACancer J Clin,2018,68(6):394-424.
[5]FERNANDEZ S V,HUANG Y,SNIDER K E,et al.Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure[J].Int J Oncol,2012,41(1):369-377.
[6]LANG PODRATZ P,DELGADO FILHO V S,LOPES P F,et al.Tributyltin impairs the reproductive cycle in female rats[J].J Toxicol Environ Health A,2012,75(16-17):1035-1046.
[7]FUCIC A,GAMULIN M,FERENCIC Z,et al.Environmental exposure to xenoestrogens and oestrogen related cancers:reproductive system,breast,lung,kidney,pancreas,and brain[J].Environ Health,2012,11(s1):s8.
[8]BERGéA,CLADIèRE M,GASPERI J,et al.Meta-analysis of environmental contamination by phthalates[J].Environ Sci Pollut Res,2013,20(11):8057-8076.
[9]FU Z,ZHAO F,CHEN K et al.Association between urinary phthalate metabolites and risk of breast cancer and uterine leiomyoma[J].Reprod Toxicol,2017,74:134-142.
[10]LEE H S,PARK E J,OH J H,et al.Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAPkinase activity[J].Biosci Biotechnol Biochem,2014,78(8):1371-1375.
[11]POIDATZ D,DOS SANTOS E,BRULéA,et al.Estrogenrelated receptor gamma modulates energy metabolism target genes in human trophoblast[J].Placenta,2012,33(9):688-695.
[12]RITTER R,SCHERINGER M,MACLEOD M,et al.Intrinsic human elimination half-lives of polychlorinated biphenyls derived from the temporal evolution of cross-sectional biomonitoring data from the United Kingdom[J].Environ Health Perspect,2011,119(2):225-231.
[13]KEZIOS K L,LIU X,CIRILLIO P M,et al.Prenatal polychlorinated biphenyl exposure is associated with decreased gestational length but not birth weight:archived samples from the Child Health and Development Studies pregnancy cohort[J].Environ Health,2012,11:49.
[14]XU C,CHEN JA,QIU Z,et al.Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl)phthalate[J].Toxicol Lett,2010,199(3):323-332.
[15]BONILLA E,DEL MAZO J,et al.Deregulation of the Sod1and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl)phthalate(MEHP)[J].Reprod Toxicol,2010,30(3):387-392.
[16]ZHANG T,LI L,QIN X S,et al.Di-(2-ethylhexyl)phthalate and bisphenol A exposure impairs mouse primordial follicle assembly in vitro[J].Environ Mol Mutagen,2014,55(4):343-353.
[17]LIU J,WANG W,ZHU J,et al.Di(2-ethylhexyl)phthalate(DEHP)influences follicular development in mice between the weaning period and maturity by interfering with ovarian development factors and microRNAs[J].Environ Toxicol,2018,33(5):535-544.
[18]MUCZYNSKI V,LECUREUIL C,MESSIAEN S,et al.Cellular and molecular effect of MEHP involving LXRαin Human Fetal testis and ovary[J].PLoS One,2012,7(10):e48266.
[19]MURATI T,?IMI?B,BROZOVIC A,et al.PCB 77 action in ovary cells-toxic effects,apoptosis induction and cell cycle analysis[J].Toxicol Mech Methods,2015,25(4):302-311.
[20]YANG Q,ZHAO Y,QIU X,et al.Association of serum levels of typical organic pollutants with polycystic ovary syndrome(PCOS):a case-control study[J].Hum Reprod,2015,30(8):1964-1973.
[21]VAGI S J,AZZIZ-BAUMGARTNER E,SJ?DIN A,et al.Exploring the potential association between brominated diphenyl ethers,polychlorinated biphenyls,organochlorine pesticides,perfluorinated compounds,phthalates,and bisphenol a in polycystic ovary syndrome:a case-control study[J].BMC Endocr Disord,2014,14:86.
[22]KANDARAKI E,CHATZIGEORGIOU A,LIVADAS S,et al.Endocrine disruptors and polycystic ovary syndrome(PCOS):elevated serum levels of bisphenol A in women with PCOS[J].J Clin Endocrinol Metab,2011,96(3):E480-E484.
[23]GORE A C,CHAPPELL V A,FENTON S E,et al.EDC-2:the endocrine society's second scientific statement on endocrine-disrupting chemicals[J].Endocr Rev,2015,36(6):E1-E150.
[24]KIM S H,CHO S,IHM H J.Possible role of phthalate in the pathogenesis of endometriosis:In vitro,animal,and human data[J].J Clin Endocrinol Metab,2015,100(12):E1502-1511.
[25]KIM J H,KIM S H,OH Y S,et al.In vitro effects of phthalate esters in human myometrial and leiomyoma cells and increased urinary level of phthalate metabolite in women with uterine leiomyoma[J].Fertil Steril,2017,107(4):1061-1069.e1.
[26]CRAIN D A,JANSSEN S J,EDWARDS T M,et al.Female reproductive disorders:the roles of endocrine-disrupting compounds and developmental timing[J].Fertil Steril,2008,90(4):911-940.
[27]POLLACK A Z,BUCK LOUIS G M,CHEN Z,et al.Bisphenol A,benzophenone-type ultraviolet filters,and phthalates in relation to uterine leiomyoma[J].Environ Res,2015,137:101-107.
[28]ISHIHARA H,YAMASHITA S,FUJII S,et al.DNA methylation marker to estimate the breast cancer cell fraction in DNAsamples[J].Med Oncol,2018,35(11):147.
[29]KANG C,LEROITH D,GALLAGHER E J.Diabetes,obesity,and breast cancer[J].Endocrinology,2018,159(11):3801-3812.
[30]CORMANIQUE T F,ALMEIDA L E,RECH C A,et al.Chronic psychological stress and its impact on the development of aggressive breast cancer[J].Einstein(S?o Paulo),2015,13(3):352-356.
[31]SHRIDHAR K,SINGH G,DEY S,et al.Dietary patterns and breast cancer risk:a multi-centre case control study among north indian women[J].Int J Environ Res Public Health,2018,15(9):1946.
[32]SIFAKIS S,ANDROUTSOPOULOS V P,TSATSAKIS A M,et al.Human exposure to endocrine disrupting chemicals:effects on the male and female reproductive systems[J].Environ Toxicol Pharmacol,2017,51:56-70.
[33]HALL J M,KORACH K S.Endocrine disrupting chemicals promote the growth of ovarian cancer cells via the ER-CXCL12-CXCR4 signaling axis[J].Mol Carcinog,2013,52(9):715-725.
[34]CHEN F P,CHIEN M H,CHERN I Y.Impact of low concentrations of phthalates on the effects of 17β-estradiol in MCF-7 breast cancer cells[J].Taiwan J Obstet Gynecol,2016,55(6):826-834.
[35]LIU S,LI S,DU Y.Polychlorinated biphenyls(PCBs)enhance metastatic properties of breast cancer cells by activating rhoassociated kinase(ROCK)[J].PLoS One,2010,5(6):e11272.
[36]SOTO A M,BRISKEN C,SCHAEBERLE C,et al.Does cancer start in the womb?Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors[J].J Mammary Gland Biol Neoplasia,2013,18(2):199-208.
[37]HOLMES A K,KOLLER K R,KIESZAK S M,et al.Casecontrol study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women[J].Int J Circumpolar Health,2014,73:25760.
[38]PARADA H J R,GAMMON M D,CHEN J,et al.Urinary phthalate metabolite concentrations and breast cancer incidence and survival following breast cancer:the long island breast cancer study project[J].Environ Health Perspect,2018,126(4):047013.
[39]SPRAGUE B L,TRENTHAM-DIETZ A,HEDMAN C J,et al.Circulating serum xenoestrogens and mammographic breast density[J].Breast Cancer Res,2013,15(3):R45
[40]DONAT-VARGAS C,?KESSON A,BERGLUND M,et al.Dietary exposure to polychlorinated biphenyls and risk of breast,endometrial and ovarian cancer in a prospective cohort[J].Br J Cancer,2016,115(9):1113-1121.
[41]WIELS?E M,KERN P,BONEFELD-J?RGENSEN EC.Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit:a case control study[J].Environ Health,2017,16(1):56.
[42]YANG O,KIM L H,WEON J I,et al.Endocrine-disrupting chemicals:review of toxicological mechanisms using molecular pathway analysis[J].J Cancer Prev,2015,20(1):12-24.
[43]NEWBOLD R R,JEFFERSON W N,PADILLA-BANKS E.Longterm adverse effects of neonatal exposure to bisphenol a on the murine female reproductive tract[J].Reprod Toxicol,2007,24(2):253-258.
[44]KIM Y S,HWANG K A,HYUN S H,et al.Bisphenol A and nonylphenol have the potential to stimulate the migration of ovarian cancer cells by inducing epithelial-mesenchymal transition via an estrogen receptor dependent pathway[J].Chem Res Toxicol,2015,28(4):662-671.
[45]YONEOKA Y,YOSHIDA H,ISHIKAWA M,et al.Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma[J].J Gynecol Oncol,2019,30:e7.
[46]LI R,YU C,GAO R,et al.Effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice[J].JHazard Mater,2012,241-242:231-240.
[47]CHEN Y,HUANG Q,CHEN Q,et al.The inflammation and estrogen metabolism impacts of polychlorinated biphenyls on endometrial cancer cells[J].Toxicol in Vitro,2015,29(2):308-313.
[48]HELMESTAM M,DAVEY E,STAVREUS-EVERS A,et al.Bisphenol A affects human endometrial endothelial cell angiogenic activity in vitro[J].Reprod Toxicol,2014,46:69-76.
[49]BROMER J G,ZHOU Y,TAYLOR M B,et al.Bisphenol-Aexposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response[J].FASEB J,2010,24(7):2273-2280
[50]REICH O,REGAUER S,SCHARF S.High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma--report of two cases[J].Eur J Gynaecol Oncol,2010,31(1):105-106.
[51]PARK M A,HWANG K A,LEE H R,et al.Cell growth of BG-1ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin Dand cyclin-dependent kinase-4 genes[J].Mol Med Rep,2012,5(3):761-766.
[52]EL-HEFNAWY T,HERNANDEZ C,STABILE L P.The endocrine disrupting alkylphenols and 4,4'-DDT interfere with estrogen conversion and clearance by mouse liver cytosol[J].Reprod Biol,2017,17(3):185-192.
[53]WANG W,CRAIG Z R,BASAVARAJAPPA M S,et al.Mono-(2-ethylhexyl)phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles[J].Biol Reprod,2012,87(6):152.
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