镉的雌性生殖毒性研究进展
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摘要
伴随我国工业化进程的快速发展,重金属镉对健康产生的危害引起社会的高度关注。随着对镉认识的不断深入,镉的雌性生殖毒性也逐渐成为镉研究领域中普遍关注的重点问题。研究表明,镉可蓄积于卵巢和胎盘中,从而影响卵巢和胎盘的结构和功能。镉具有雌激素样作用,其内分泌干扰作用可能是镉雌性生殖毒性的重要机制之一。本文就近年来镉对雌性生殖系统影响及其作用机制的研究进行综述,为维护妇女儿童的身体健康提供理论研究依据。
With the rapid development of industrialization process, the harmful health effects of cadmium become a public concern. With the deepening understanding of cadmium, the female reproductive toxicity of cadmium also becomes a focus of cadmium research. Studies have shown that cadmium can accumulate in ovary and placenta, thus affecting the structure and function of ovary and placenta. Cadmium has an estrogen-like effect and its endocrine interference may be one of the important mechanisms of its female reproductive toxicity. This paper reviewed the reproductive toxicity of cadmium on female and its action mechanism, aiming to provide a theoretical basis for safeguarding the health of women and children.
With the rapid development of industrialization process, the harmful health effects of cadmium become a public concern. With the deepening understanding of cadmium, the female reproductive toxicity of cadmium also becomes a focus of cadmium research. Studies have shown that cadmium can accumulate in ovary and placenta, thus affecting the structure and function of ovary and placenta. Cadmium has an estrogen-like effect and its endocrine interference may be one of the important mechanisms of its female reproductive toxicity. This paper reviewed the reproductive toxicity of cadmium on female and its action mechanism, aiming to provide a theoretical basis for safeguarding the health of women and children.
引文
[1]ZHU J Q,LIU Y,ZHANG J H,et al.Cadmium exposure of female mice impairs the meiotic maturation of oocytes and subsequent embryonic development[J].Toxicol Sci,2018,164(1):289-299.
[2]黄秋驰,王燕燕,杨燕,等.环境中镉暴露对生殖系统影响的研究进展[J].环境卫生学杂志,2014,4(4):413-417.
[3]RAFATI-RAHIMZADEH M,RAFATI-RAHIMZADEH M,KAZEMIS,et al.Cadmium toxicity and treatment:An update[J].Caspian J Intern Med,2017,8(3):135-145.
[4]DE ANGELIS C,GALDIERO M,PIVONELLO C,et al.The environment and male reproduction:The effect of cadmium exposure on reproductive function and its implication in fertility[J].Reprod Toxicol,2017,73:105-127.
[5]ZHAO L L,RU Y F,LIU M,et al.Reproductive effects of cadmium on sperm function and early embryonic development in vitro[J].PLoS One,2017,12(11):e0186727.
[6]DE FRANCISCIS P,IANNIELLO R,LABRIOLA D,et al.Environmental pollution due to cadmium:measure of semen quality as a marker of exposure and correlation with reproductive potential[J].Clin Exp Obstet Gynecol,2015,42(6):767-770.
[7]NASIADEK M,SKRZYPI?SKA-GAWRYSIAK M,DARAGóA,et al.Involvement of oxidative stress in the mechanism of cadmium-induced toxicity on rat uterus[J].Environ Toxicol Pharmacol,2014,38(2):364-373.
[8]NASIADEK M,DANILEWICZ M,SITAREK K,et al.The effect of repeated cadmium oral exposure on the level of sex hormones,estrous cyclicity,and endometrium morphometry in female rats[J].Environ Sci Pollut Res Int,2018,25(28):28025-28038.
[9]RZYMSKI P,RZYMSKI P,TOMCZYK K,et al.Metal status in human endometrium:relation to cigarette smoking and histological lesions[J].Environ Res,2014,132:328-333.
[10]SAROJ V K,NAKADE U P,SHARMA A,et al.Dose-dependent differential effects of in vivo exposure of cadmium on myometrial activity in rats:involvement of VDCC and Ca2+-mimicking pathways[J].Biol Trace Elem Res,2018,181(2):272-280.
[11]WANG Y,WANG X,WANG Y,et al.Effect of cadmium on cellular ultrastructure in mouse ovary[J].Ultrastruct Pathol,2015,39(5):324-328.
[12]TANRIKUT E,KARAER A,CELIK O,et al.Role of endometrial concentrations of heavy metals(cadmium,lead,mercury and arsenic)in the aetiology of unexplained infertility[J].Eur J Obstet Gynecol Reprod Biol,2014,179:187-190.
[13]POLLACK A Z,SJAARDA L,AHRENS K A,et al.Association of cadmium,lead and mercury with paraoxonase 1 activity in women[J].PLoS One,2014,9(3):e92152.
[14]SAPMAZ-METIN M,TOPCU-TARLADACALISIR Y,KURT-OMURLU I,et al.A morphological study of uterine alterations in mice due to exposure to cadmium[J].Biotech Histochem,2017,92(4):264-273.
[15]LI Z,LI T,LENG Y,et al.Hormonal changes and folliculogenesis in female offspring of rats exposed to cadmium during gestation and lactation[J].Environ Pollut,2018,238:336-347.
[16]ZHANG W,WU T,ZHANG C,et al.Cadmium exposure in newborn rats ovary induces developmental disorders of primordial follicles and the differential expression of SCF/c-kit gene[J].Toxicol Lett,2017,280:20-28.
[17]WENG S,WANG W,LI Y,et al.Continuous cadmium exposure from weaning to maturity induces downregulation of ovarian follicle development-related SCF/c-kit gene expression and the corresponding changes of DNAmethylation/microRNA pattern[J].Toxicol Lett,2014,225(3):367-377.
[18]刘洋.镉对小鼠卵母细胞成熟和早期胚胎发育的影响[D].扬州:扬州大学,2017.
[19]刘莉莉.低剂量镉暴露对大鼠生殖发育毒性及胎盘屏障相关的蛋白质组学研究[D].广州:南方医科大学,2016.
[20]ZHANG G B,WANG H,HU J,et al.Cadmium-induced neural tube defects and fetal growth restriction:Association with disturbance of placental folate transport[J].Toxicol Appl Pharmacol,2016,306:79-85.
[21]WANG H,WANG Y,BO Q L,et al.Maternal cadmium exposure reduces placental zinc transport and induces fetal growth restriction in mice[J].Reprod Toxicol,2016,63:174-182.
[22]王华.孕期母体镉暴露与胎儿生长受限的关联及其机制研究[D].合肥:安徽医科大学,2015.
[23]马合红,张俊峰,杨双燕,等.镉对孕鼠生殖毒性及胎鼠发育毒性的作用研究[J].广西医科大学学报,2016,33(3):405-408.
[24]刘莉莉,周珊宇,邓莹玉,等.ABCB4蛋白介导低剂量镉暴露对大鼠胎盘毒作用探讨[J].中国职业医学,2016,43(5):513-518.
[25]ERBOGA M,KANTER M.Effect of cadmium on trophoblast cell proliferation and apoptosis in different gestation periods of rat placenta[J].Biol Trace Elem Res,2016,169(2):285-293.
[26]WANG Z,WANG H,XU Z M,et al.Cadmium-induced teratogenicity:association with ROS-mediated endoplasmic reticulum stress in placenta[J].Toxicol Appl Pharmacol,2012,259(2):236-247.
[27]胡隽,朱华龙,熊永伟,等.氯化镉对体外培养的人胎盘滋养细胞增殖与凋亡的影响[J].毒理学杂志,2018,32(4):322-326.
[28]GARCIA-MORALES P,SACEDA M,KENNEY N,et al.Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells[J].J Biol Chem,1994,269(24):16896-16901.
[29]STRUMYLAITE L,KREGZDYTE R,BOGUSEVICIUS A,et al.Association between cadmium and breast cancer risk according to estrogen receptor and human epidermal growth factor receptor 2:epidemiological evidence[J].Breast Cancer Res Treat,2014,145(1):225-232.
[30]ITOH H,IWASAKI M,SAWADA N,et al.Dietary cadmium intake and breast cancer risk in Japanese women:a casecontrol study[J].Int J Hyg Environ Health,2014,217(1):70-77.
[31]LIU R,NELSON D O,HURLEY S,et al.Residential exposure to estrogen disrupting hazardous air pollutants and breast cancer risk:the California teachers study[J].Epidemiology,2015,26(3):365-373.
[32]NAGATA C,NAGAO Y,NAKAMURA K,et al.Cadmium exposure and the risk of breast cancer in Japanese women[J].Breast Cancer Res Treat,2013,138(1):235-239.
[33]JULIN B,WOLK A,BERGKVIST L,et al.Dietary cadmium exposure and risk of postmenopausal breast cancer:a population-based prospective cohort study[J].Cancer Res,2012,72(6):1459-1466.
[34]RAHIM F,JALALI A,TANGESTANI R.Breast cancer frequency and exposure to cadmium:a meta-analysis and systematic review[J].Asian Pac J Cancer Prev,2013,14(7):4283-4287.
[35]VAN MAELE-FABRY G,LOMBAERT N,LISON D.Dietary ex p o s u re to ca d m i u m a n d r i s k o f b re a st ca n c e r i n postmenopausal women:A systematic review and metaanalysis[J].Environ Int,2016,86:1-13.
[36]凌晓斐,胥可,孙亚昕,等.镉通过类雌激素样作用促进人乳腺癌MCF-7细胞增殖[J].环境与职业医学,2018,35(4):356-360.
[37]李碧云,李志鹏,蔡日东,等.镉对MCF-7细胞雌激素受体和miRNA表达作用研究[J].中国职业医学,2018,45(1):30-34.
[38]PONCE E,AQUINO N B,LOUIE M C.Chronic cadmium exposure stimulates SDF-1 expression in an ERαdependent manner[J].PLoS One,2013,8(8):e72639.
[39]MCELROY J A,KRUSE R L,GUTHRIE J,et al.Cadmium exposure and endometrial cancer risk:A large midwestern U.S.population-based case-control study[J].PLoS One,2017,12(7):e0179360.
[40]张俊峰,马合红,郑新英,等.镉对雌性大鼠生殖系统损害的研究[J].中国妇幼保健,2016,31(14):2947-2949.
[41]RZYMSKI P,NIEDZIELSKI P,RZYMSKI P,et al.Metal accumulation in the human uterus varies by pathology and smoking status[J].Fertil Steril,2016,105(6):1511-1518.e3.
[42]LAFUENTE A.The hypothalamic-pituitary-gonadal axis is target of cadmium toxicity.An update of recent studies and potential therapeutic approaches[J].Food Chem Toxicol,2013,59:395-404.
[43]LI S,WANG M,YANG B,et al.A novel method applied in determination and assessment of trace amount of lead and cadmium in rice from four provinces,China[J].PLoS One,2014,9(9):e107733.
[44]NAGATA C,KONISHI K,GOTO Y,et al.Associations of urinary cadmium with circulating sex hormone levels in preand postmenopausal Japanese women[J].Environ Res,2016,150:82-87.
[45]张纯,张帆,何联,等.镉对未成年雌性大鼠卵巢组织激素分泌的影响[J].山东医药,2013,53(7):52-53.
[46]LU C L,TANG S,MENG Z J,et al.Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure[J].J Biomed Sci,2014,21:51.
[47]李爽,王瑞俭,高凌.镉对斑马鱼卵巢的毒性效应和子代响应[J].北华大学学报(自然科学版),2018,19(4):532-535.
[48]LIU G,ZHANG S,YANG K,et al.Toxicity of perfluorooctane sulfonate and perfluorooctanoic acid to Escherichia coli:Membrane disruption,oxidative stress,and DNA damage induced cell inactivation and/or death[J].Environ Pollut,2016,214:806-815.
[49]刘洋,王兰,孙敏.慢性镉暴露对斑马鱼卵巢组织的氧化损伤和子代发育的母源影响[J].生物技术通讯,2017,28(3):301-307.
[50]DHARMADASA P,KIM N,THUNDERS M.Maternal cadmium exposure and impact on foetal gene expression through methylation changes[J].Food Chem Toxicol,2017,109:714-720.
[51]吴中强.妊娠期镉胁迫致小鼠胎儿宫内生长受限小鼠胎盘的DNA甲基化研究[D].太原:山西大学,2017.
[52]吴停停,谢美美,罗凌凤,等.大鼠卵巢镉暴露对DNA甲基转移酶表达的实验研究[J].中国预防医学杂志,2016,17(6):401-404.
[53]MA P,SCHULTZ R M.Histone deacetylase 2(HDAC2)regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse[J].PLoS Genet,2013,9(3):e1003377.
[54]SATARUG S,GARRETT S H,SENS M A,et al.Cadmium,environmental exposure,and health outcomes[J].Environ Health Perspect,2010,118(2):182-190.
[2]黄秋驰,王燕燕,杨燕,等.环境中镉暴露对生殖系统影响的研究进展[J].环境卫生学杂志,2014,4(4):413-417.
[3]RAFATI-RAHIMZADEH M,RAFATI-RAHIMZADEH M,KAZEMIS,et al.Cadmium toxicity and treatment:An update[J].Caspian J Intern Med,2017,8(3):135-145.
[4]DE ANGELIS C,GALDIERO M,PIVONELLO C,et al.The environment and male reproduction:The effect of cadmium exposure on reproductive function and its implication in fertility[J].Reprod Toxicol,2017,73:105-127.
[5]ZHAO L L,RU Y F,LIU M,et al.Reproductive effects of cadmium on sperm function and early embryonic development in vitro[J].PLoS One,2017,12(11):e0186727.
[6]DE FRANCISCIS P,IANNIELLO R,LABRIOLA D,et al.Environmental pollution due to cadmium:measure of semen quality as a marker of exposure and correlation with reproductive potential[J].Clin Exp Obstet Gynecol,2015,42(6):767-770.
[7]NASIADEK M,SKRZYPI?SKA-GAWRYSIAK M,DARAGóA,et al.Involvement of oxidative stress in the mechanism of cadmium-induced toxicity on rat uterus[J].Environ Toxicol Pharmacol,2014,38(2):364-373.
[8]NASIADEK M,DANILEWICZ M,SITAREK K,et al.The effect of repeated cadmium oral exposure on the level of sex hormones,estrous cyclicity,and endometrium morphometry in female rats[J].Environ Sci Pollut Res Int,2018,25(28):28025-28038.
[9]RZYMSKI P,RZYMSKI P,TOMCZYK K,et al.Metal status in human endometrium:relation to cigarette smoking and histological lesions[J].Environ Res,2014,132:328-333.
[10]SAROJ V K,NAKADE U P,SHARMA A,et al.Dose-dependent differential effects of in vivo exposure of cadmium on myometrial activity in rats:involvement of VDCC and Ca2+-mimicking pathways[J].Biol Trace Elem Res,2018,181(2):272-280.
[11]WANG Y,WANG X,WANG Y,et al.Effect of cadmium on cellular ultrastructure in mouse ovary[J].Ultrastruct Pathol,2015,39(5):324-328.
[12]TANRIKUT E,KARAER A,CELIK O,et al.Role of endometrial concentrations of heavy metals(cadmium,lead,mercury and arsenic)in the aetiology of unexplained infertility[J].Eur J Obstet Gynecol Reprod Biol,2014,179:187-190.
[13]POLLACK A Z,SJAARDA L,AHRENS K A,et al.Association of cadmium,lead and mercury with paraoxonase 1 activity in women[J].PLoS One,2014,9(3):e92152.
[14]SAPMAZ-METIN M,TOPCU-TARLADACALISIR Y,KURT-OMURLU I,et al.A morphological study of uterine alterations in mice due to exposure to cadmium[J].Biotech Histochem,2017,92(4):264-273.
[15]LI Z,LI T,LENG Y,et al.Hormonal changes and folliculogenesis in female offspring of rats exposed to cadmium during gestation and lactation[J].Environ Pollut,2018,238:336-347.
[16]ZHANG W,WU T,ZHANG C,et al.Cadmium exposure in newborn rats ovary induces developmental disorders of primordial follicles and the differential expression of SCF/c-kit gene[J].Toxicol Lett,2017,280:20-28.
[17]WENG S,WANG W,LI Y,et al.Continuous cadmium exposure from weaning to maturity induces downregulation of ovarian follicle development-related SCF/c-kit gene expression and the corresponding changes of DNAmethylation/microRNA pattern[J].Toxicol Lett,2014,225(3):367-377.
[18]刘洋.镉对小鼠卵母细胞成熟和早期胚胎发育的影响[D].扬州:扬州大学,2017.
[19]刘莉莉.低剂量镉暴露对大鼠生殖发育毒性及胎盘屏障相关的蛋白质组学研究[D].广州:南方医科大学,2016.
[20]ZHANG G B,WANG H,HU J,et al.Cadmium-induced neural tube defects and fetal growth restriction:Association with disturbance of placental folate transport[J].Toxicol Appl Pharmacol,2016,306:79-85.
[21]WANG H,WANG Y,BO Q L,et al.Maternal cadmium exposure reduces placental zinc transport and induces fetal growth restriction in mice[J].Reprod Toxicol,2016,63:174-182.
[22]王华.孕期母体镉暴露与胎儿生长受限的关联及其机制研究[D].合肥:安徽医科大学,2015.
[23]马合红,张俊峰,杨双燕,等.镉对孕鼠生殖毒性及胎鼠发育毒性的作用研究[J].广西医科大学学报,2016,33(3):405-408.
[24]刘莉莉,周珊宇,邓莹玉,等.ABCB4蛋白介导低剂量镉暴露对大鼠胎盘毒作用探讨[J].中国职业医学,2016,43(5):513-518.
[25]ERBOGA M,KANTER M.Effect of cadmium on trophoblast cell proliferation and apoptosis in different gestation periods of rat placenta[J].Biol Trace Elem Res,2016,169(2):285-293.
[26]WANG Z,WANG H,XU Z M,et al.Cadmium-induced teratogenicity:association with ROS-mediated endoplasmic reticulum stress in placenta[J].Toxicol Appl Pharmacol,2012,259(2):236-247.
[27]胡隽,朱华龙,熊永伟,等.氯化镉对体外培养的人胎盘滋养细胞增殖与凋亡的影响[J].毒理学杂志,2018,32(4):322-326.
[28]GARCIA-MORALES P,SACEDA M,KENNEY N,et al.Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells[J].J Biol Chem,1994,269(24):16896-16901.
[29]STRUMYLAITE L,KREGZDYTE R,BOGUSEVICIUS A,et al.Association between cadmium and breast cancer risk according to estrogen receptor and human epidermal growth factor receptor 2:epidemiological evidence[J].Breast Cancer Res Treat,2014,145(1):225-232.
[30]ITOH H,IWASAKI M,SAWADA N,et al.Dietary cadmium intake and breast cancer risk in Japanese women:a casecontrol study[J].Int J Hyg Environ Health,2014,217(1):70-77.
[31]LIU R,NELSON D O,HURLEY S,et al.Residential exposure to estrogen disrupting hazardous air pollutants and breast cancer risk:the California teachers study[J].Epidemiology,2015,26(3):365-373.
[32]NAGATA C,NAGAO Y,NAKAMURA K,et al.Cadmium exposure and the risk of breast cancer in Japanese women[J].Breast Cancer Res Treat,2013,138(1):235-239.
[33]JULIN B,WOLK A,BERGKVIST L,et al.Dietary cadmium exposure and risk of postmenopausal breast cancer:a population-based prospective cohort study[J].Cancer Res,2012,72(6):1459-1466.
[34]RAHIM F,JALALI A,TANGESTANI R.Breast cancer frequency and exposure to cadmium:a meta-analysis and systematic review[J].Asian Pac J Cancer Prev,2013,14(7):4283-4287.
[35]VAN MAELE-FABRY G,LOMBAERT N,LISON D.Dietary ex p o s u re to ca d m i u m a n d r i s k o f b re a st ca n c e r i n postmenopausal women:A systematic review and metaanalysis[J].Environ Int,2016,86:1-13.
[36]凌晓斐,胥可,孙亚昕,等.镉通过类雌激素样作用促进人乳腺癌MCF-7细胞增殖[J].环境与职业医学,2018,35(4):356-360.
[37]李碧云,李志鹏,蔡日东,等.镉对MCF-7细胞雌激素受体和miRNA表达作用研究[J].中国职业医学,2018,45(1):30-34.
[38]PONCE E,AQUINO N B,LOUIE M C.Chronic cadmium exposure stimulates SDF-1 expression in an ERαdependent manner[J].PLoS One,2013,8(8):e72639.
[39]MCELROY J A,KRUSE R L,GUTHRIE J,et al.Cadmium exposure and endometrial cancer risk:A large midwestern U.S.population-based case-control study[J].PLoS One,2017,12(7):e0179360.
[40]张俊峰,马合红,郑新英,等.镉对雌性大鼠生殖系统损害的研究[J].中国妇幼保健,2016,31(14):2947-2949.
[41]RZYMSKI P,NIEDZIELSKI P,RZYMSKI P,et al.Metal accumulation in the human uterus varies by pathology and smoking status[J].Fertil Steril,2016,105(6):1511-1518.e3.
[42]LAFUENTE A.The hypothalamic-pituitary-gonadal axis is target of cadmium toxicity.An update of recent studies and potential therapeutic approaches[J].Food Chem Toxicol,2013,59:395-404.
[43]LI S,WANG M,YANG B,et al.A novel method applied in determination and assessment of trace amount of lead and cadmium in rice from four provinces,China[J].PLoS One,2014,9(9):e107733.
[44]NAGATA C,KONISHI K,GOTO Y,et al.Associations of urinary cadmium with circulating sex hormone levels in preand postmenopausal Japanese women[J].Environ Res,2016,150:82-87.
[45]张纯,张帆,何联,等.镉对未成年雌性大鼠卵巢组织激素分泌的影响[J].山东医药,2013,53(7):52-53.
[46]LU C L,TANG S,MENG Z J,et al.Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure[J].J Biomed Sci,2014,21:51.
[47]李爽,王瑞俭,高凌.镉对斑马鱼卵巢的毒性效应和子代响应[J].北华大学学报(自然科学版),2018,19(4):532-535.
[48]LIU G,ZHANG S,YANG K,et al.Toxicity of perfluorooctane sulfonate and perfluorooctanoic acid to Escherichia coli:Membrane disruption,oxidative stress,and DNA damage induced cell inactivation and/or death[J].Environ Pollut,2016,214:806-815.
[49]刘洋,王兰,孙敏.慢性镉暴露对斑马鱼卵巢组织的氧化损伤和子代发育的母源影响[J].生物技术通讯,2017,28(3):301-307.
[50]DHARMADASA P,KIM N,THUNDERS M.Maternal cadmium exposure and impact on foetal gene expression through methylation changes[J].Food Chem Toxicol,2017,109:714-720.
[51]吴中强.妊娠期镉胁迫致小鼠胎儿宫内生长受限小鼠胎盘的DNA甲基化研究[D].太原:山西大学,2017.
[52]吴停停,谢美美,罗凌凤,等.大鼠卵巢镉暴露对DNA甲基转移酶表达的实验研究[J].中国预防医学杂志,2016,17(6):401-404.
[53]MA P,SCHULTZ R M.Histone deacetylase 2(HDAC2)regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse[J].PLoS Genet,2013,9(3):e1003377.
[54]SATARUG S,GARRETT S H,SENS M A,et al.Cadmium,environmental exposure,and health outcomes[J].Environ Health Perspect,2010,118(2):182-190.
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