镉对胚胎/胎儿发育的损害作用及其机制
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摘要
镉对生态环境和人群健康的危害受到广泛关注。以往研究主要关注成年期镉暴露对肝脏、肾脏、肺脏、大脑和睾丸等脏器的损害作用,但对子代及其远期损害作用的研究甚少。近年来,孕期母体环境镉暴露与胚胎/胎儿发育损伤的关联研究已成为当前重要的公共卫生问题,镉的发育毒性作用及其机制已有大量研究报道。众多研究资料显示,孕期母体镉暴露能够引起胚胎/胎儿死亡、胎儿畸形和胎儿生长受限等。此外,出生前镉暴露还可以引起子代智力低下、情感障碍、心血管疾病、雄性生殖障碍等慢性疾病高发。镉引起胚胎/胎儿发育损伤的机制主要包括母源性机制、胎盘机制和胎儿损伤机制等。因此,本文着重综述了镉对胚胎/胎儿发育的损害作用及其机制的研究进展。
The adverse effects of cadmium on ecosystem and human health have attracted worldwideattention. Previous studies have focused mainly on the toxic effects of cadmium exposure inadulthood on liver, kidney, lung, brain, and testis; however, there are few studies on progenyand its long-term effects. Recently, the association between maternal cadmium exposure duringpregnancy and embryonic/fetal dysplasia has become a hot topic in public health as a lot ofstudies have reported cadmium-induced developmental toxicity and its mechanism. Otherstudies have shown that maternal cadmium exposure during pregnancy can cause fetal death,fetal malformation, and fetal growth restriction. In addition, prenatal cadmium exposure canlead to lower IQ, mood disorders, cardiovascular diseases, male reproductive impairments, andother chronic diseases. The mechanisms of cadmium causing embryonic/fetal developmentinjury mainly include maternal mechanism, placental mechanism, and fetal injury mechanism.Therefore, the adverse effects of cadmium on embryonic and fetal development and itsmechanism were summarized in this review.
The adverse effects of cadmium on ecosystem and human health have attracted worldwideattention. Previous studies have focused mainly on the toxic effects of cadmium exposure inadulthood on liver, kidney, lung, brain, and testis; however, there are few studies on progenyand its long-term effects. Recently, the association between maternal cadmium exposure duringpregnancy and embryonic/fetal dysplasia has become a hot topic in public health as a lot ofstudies have reported cadmium-induced developmental toxicity and its mechanism. Otherstudies have shown that maternal cadmium exposure during pregnancy can cause fetal death,fetal malformation, and fetal growth restriction. In addition, prenatal cadmium exposure canlead to lower IQ, mood disorders, cardiovascular diseases, male reproductive impairments, andother chronic diseases. The mechanisms of cadmium causing embryonic/fetal developmentinjury mainly include maternal mechanism, placental mechanism, and fetal injury mechanism.Therefore, the adverse effects of cadmium on embryonic and fetal development and itsmechanism were summarized in this review.
引文
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[38]WANG F,ZHANG Q,ZHANG X,et al.Preeclampsia induced by cadmium in rats is related to abnormal local glucocorticoid synthesis in placenta[J].Reprod Biol Endocrinol,2014,12:77.
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[43]DEMIR H,KANTER M,COSKUN O,et al.Effect of black cumin(Nigella sativa)on heart rate,some hematological values,and pancreaticβ-cell damage in cadmium-treated rats[J].Biol Trace Elem Res,2006,110(2):151-162.
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[2]THOMPSON J,BANNIGAN J.Cadmium:toxic effects on the reproductive system and the embryo[J].Reprod Toxicol,2008,25(3):304-315.
[3]CHATZI L,IERODIAKONOU D,MARGETAKI K,et al.Associations of prenatal exposure to cadmium with child growth,obesity,and cardiometabolic traits[J].Am JEpidemiol,2018,188(1):141-150.
[4]HUANG K,LI H,ZHANG B,et al.Prenatal cadmium exposure and preterm low birth weight in China[J].J Expo Sci Environ Epidemiol,2017,27(5):491-496.
[5]KAUR S.Lead and cadmium in maternal blood,umbilical cord blood,amniotic fluid and placenta of cows and buffaloes after foetal death(abortion)and after normal parturition[J].Sci Total Environ,1989,79(3):287-290.
[6]SELYPES A,LORENCZ R,BERENCSI G,et al.The effect of prednisolone on the foetotoxicity of cadmium in pregnant mice[J].J Appl Toxicol,1986,6(1):47-48.
[7]SALTZMAN R A,MILLER R K,DI SANT'AGNESE P A.Cadmium exposure on day 12 of gestation in the Wistar rat:distribution,uteroplacental blood flow,and fetal viability[J].Teratology,1989,39(1):19-30.
[8]KUNDAK A A,PEKTAS A,ZENCIROGLU A,et al.Do toxic metals and trace elements have a role in the pathogenesis of conotruncal heart malformations?[J].Cardiol Young,2017,27(2):312-317.
[9]JIN X,TIAN X,LIU Z,et al.Maternal exposure to arsenic and cadmium and the risk of congenital heart defects in offspring[J].Reprod Toxicol,2016,59:109-116.
[10]PANIAGUA-CASTRO N,ESCALONA-CARDOSO G,CHAMORRO-CEVALLOS G.Glycine reduces cadmium-induced teratogenic damage in mice[J].Reprod Toxicol,2007,23(1):92-97.
[11]ROBINSON J F,YU X,HONG S,et al.Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation[J].Toxicol Sci,2009,107(1):206-219.
[12]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.
[13]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.
[14]KIPPLER M,WAGATSUMA Y,RAHMAN A,et al.Environmental exposure to arsenic and cadmium during pregnancy and fetal size:a longitudinal study in rural Bangladesh[J].Reprod Toxicol,2012,34(4):504-511.
[15]MENAI M,HEUDE B,SLAMA R,et al.Association between maternal blood cadmium during pregnancy and birth weight and the risk of fetal growth restriction:the EDEN mother-child cohort study[J].Reprod Toxicol,2012,34(4):622-627.
[16]IKEH-TAWARI E P,ANETOR J I,CHARLES-DAVIES M A.Cadmium level in pregnancy,influence on neonatal birth weight and possible amelioration by some essential trace elements[J].Toxicol Int,2013,20(1):108-112.
[17]AL-SALEH I,SHINWARI N,MASHHOUR A,et al.Birth outcome measures and maternal exposure to heavy metals(lead,cadmium and mercury)in Saudi Arabian population[J].Int J Hyg Environ Health,2014,217(2-3):205-218.
[18]ZHANG Y L,ZHAO Y C,WANG J X,et al.Effect of environmental exposure to cadmium on pregnancy outcome and fetal growth:a study on healthy pregnant women in China[J].J Environ Sci Health A Tox Hazard Subst Environ Eng,2004,39(9):2507-2515.
[19]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.
[20]JI Y L,WANG H,LIU P,et al.Effects of maternal cadmium exposure during late pregnant period on testicular steroidogenesis in male offspring[J].Toxicol Lett,2011,205(1):69-78.
[21]SABRA S,MALMQVIST E,SABORIT A,et al.Heavy metals exposure levels and their correlation with different clinical forms of fetal growth restriction[J].PLoS One,2017,12(10):e0185645.
[22]VISENTIN S,GRUMOLATO F,NARDELLI G B,et al.Early origins of adult disease:low birth weight and vascular remodeling[J].Atherosclerosis,2014,237(2):391-399.
[23]LONGO S,BOLLANI L,DECEMBRINO L,et al.Short-term and long-term sequelae in intrauterine growth retardation(IUGR)[J].J Matern Fetal Neonatal Med,2013,26(3):222-225.
[24]SZOSTAK-WEGIEREK D,SZAMOTULSKA K.Fetal development and risk of cardiovascular diseases and diabetes type 2 in adult life[J].Med WiekuRozwoj,2011,15(3):203-215.
[25]KERNS S L,GUEVARA-AGUIRRE J,ANDREW S,et al.A novel variant in CDKN1C is associated with intrauterine growth restriction,short stature,and early-adulthood-onset diabetes[J].J Clin Endocrinol Metab,2014,99(10):E2117-2122.
[26]SIOEN I,DEN HOND E,NELEN V,et al.Prenatal exposure to environmental contaminants and behavioural problems at age 7-8 years[J].Environ Int,2013,59:225-231.
[27]KIPPLER M,TOFAIL F,HAMADANI J D,et al.Early-life cadmium exposure and child development in 5-year-old girls and boys:a cohort study in rural bangladesh[J].Environ Health Perspect,2012,120(10):1462-1468.
[28]GUO M Y,WANG H,CHEN Y H,et al.N-acetylcysteine alleviates cadmium-induced placental endoplasmic reticulum stress and fetal growth restriction in mice[J].PLoS One,2018,13(1):e0191667.
[29]JEONG K S,PARK H,HA E,et al.Performance IQ in children is associated with blood cadmium concentration in early pregnancy[J].J Trace Elem Med Biol,2015,30:107-111.
[30]RONCO A M,MONTENEGRO M,CASTILLO P,et al.Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring[J].Toxicol Appl Pharmacol,2011,251(2):137-145.
[31]KUHNERT B R,KUHNERT P M,LAZEBNIK N,et al.The effect of maternal smoking on the relationship between maternal and fetal zinc status and infant birth weight[J].J Am Coll Nutr,1988,7(4):309-316.
[32]SCHEUHAMMER A M,ONOSAKA S,RODGERS K,et al.The interaction of zinc and cadmium in the synthesis of hepatic metallothionein in rats[J].Toxicology,1985,36(2/3):101-108.
[33]LALL S B,DAN G.Role of corticosteroids in cadmium induced immunotoxicity[J].Drug Chem Toxicol,1999,22(2):401-409.
[34]HIDALGO J,ARMARIO A.Effect of Cd administration on the pituitary-adrenal axis[J].Toxicology,1987,45(1):113-116.
[35]STAUD F,MAZANCOVáK,MIK?íK I,et al.Corticosterone transfer and metabolism in the dually perfused rat placenta:effect of 11β-hydroxysteroid dehydrogenase type2[J].Placenta,2006,27(2/3):171-180.
[36]YANG K,JULAN L,RUBIO F,et al.Cadmium reduces11β-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells[J].Am JPhysiol Endocrinol Metab,2006,290(1):E135-E142.
[37]AABIDHA P M,CHERIAN A G,PAUL E,et al.Maternal and fetal outcome in pre-eclampsia in a secondary care hospital in South India[J].J Family Med Prim Care,2015,4(2):257-260.
[38]WANG F,ZHANG Q,ZHANG X,et al.Preeclampsia induced by cadmium in rats is related to abnormal local glucocorticoid synthesis in placenta[J].Reprod Biol Endocrinol,2014,12:77.
[39]FENG W,CUI X,LIU B,et al.Association of urinary metal profiles with altered glucose levels and diabetes risk:a population-based study in China[J].PLoS One,2015,10(4):e0123742.
[40]ROMANO M E,ENQUOBAHRIE D A,SIMPSON C D,et al.Acase-cohort study of cadmium body burden and gestational diabetes mellitus in american women[J].Environ Health Perspect,2015,123(10):993-998.
[41]WALLIA A,ALLEN N B,BADON S,et al.Association between urinary cadmium levels and prediabetes in the NHANES2005-2010 population[J].Int J Hyg Environ Health,2014,217(8):854-860.
[42]PENG S,LIU L,ZHANG X,et al.A nested case-control study indicating heavy metal residues in meconium associate with maternal gestational diabetes mellitus risk[J].Environ Health,2015,14:19.
[43]DEMIR H,KANTER M,COSKUN O,et al.Effect of black cumin(Nigella sativa)on heart rate,some hematological values,and pancreaticβ-cell damage in cadmium-treated rats[J].Biol Trace Elem Res,2006,110(2):151-162.
[44]FINE E L,HORAL M,CHANG T I,et al.Evidence that elevated glucose causes altered gene expression,apoptosis,and neural tube defects in a mouse model of diabetic pregnancy[J].Diabetes,1999,48(12):2454-2462.
[45]ORNOY A.Prenatal origin of obesity and their complications:gestational diabetes,maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia[J].Reprod Toxicol,2011,32(2):205-212.
[46]LARQUéE,RUIZ-PALACIOS M,KOLETZKO B.Placental regulation of fetal nutrient supply[J].CurrOpin Clin NutrMetab Care,2013,16(3):292-297.
[47]HSIAO E Y,PATTERSON P H.Placental regulation ofmaternalfetal interactions and brain development[J].DevNeurobiol,2012,72(10):1317-1326.
[48]NEWBERN D,FREEMARK M.Placental hormones and thecontrol of maternal metabolism and fetal growth[J].Curr Opin Endocrinol Diabetes Obes,2011,18(6):409-416.
[49]LIN S,HUO X,ZHANG Q,et al.Short placental telomere was associated with cadmium pollution in an electronic waste recycling Town in China[J].PLoS One,2013,8(4):e60815.
[50]RONCO A M,ARGUELLO G,MU?OZ L,et al.Metals content in placentas from moderate cigarette consumers:correlation with newborn birth weight[J].Biometals,2005,18(3):233-241.
[51]SAKAMOTO M,YASUTAKE A,DOMINGO J L,et al.Relationships between trace element concentrations in chorionic tissue of placenta and umbilical cord tissue:potential use as indicators for prenatal exposure[J].Environ Int,2013,60:106-111.
[52]KIPPLER M,HOQUE A M,RAQIB R,et al.Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus[J].Toxicol Lett,2010,192(2):162-168.
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