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Increased DMT-1 expression in placentas of women living in high-Cd-contaminated areas of Thailand

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Abstract

Cadmium (Cd) is a toxic heavy metal and contamination was reported in soil and rice in several areas of Thailand. Humans are normally exposed to environmental Cd, leading to gradual Cd accumulation in their bodies, including the placenta. DMT-1 is a divalent metal transporter which is found in placental tissue and plays a vital role in the transportation of Fe2+ and Cd2+. This study investigated DMT-1 protein and mRNA expressions in full term human placentas comparing those from high-Cd-contaminated areas (high-Cd group) and low-Cd-contaminated areas (low-Cd group), n = 6 per group. The maternal blood Cd (B-Cd) and placental Cd (P-Cd) of the high-Cd group was significantly raised in comparison with those in the low-Cd group. DMT-1 in the fetal portion of the placentas was localized in the apical and basal portions of the cytoplasm of the syncytiotrophoblastic cells, the endothelium of fetal capillaries which is functional structure of the placental barrier, and was also found in the cytoplasm of Hofbauer cells. Moreover, DMT-1 localization in the maternal portion was also detected in most decidual cells. In addition, the DMT-1 protein and mRNA expressions in the high-Cd group were significantly higher than those in the low-Cd group. Therefore, we suggest that pregnant women, who are exposed to environmental Cd, show an increased level of Cd in their maternal blood and this Cd can accumulate in the placenta. Intracellular Cd may induce DMT-1 mRNA transcription which further translates into DMT-1 protein, which can then function as a reciprocal Cd transporter in placental tissue.

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References

  • Andrews GK (2001) Cellular zinc sensors: MTF-1 regulation of gene expression. Biometals 14:223–237

    Article  CAS  Google Scholar 

  • Bannon DI, Abounader R, Lees PS, Bressler JP (2003) Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Phys Cell Phys 284:C44–C50

    Article  CAS  Google Scholar 

  • Chong WS, Kwan PC, Chan LY, Chiu PY, Cheung TK, Lau TK (2005) Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues. Hum Reprod 20:3532–3538

    Article  CAS  Google Scholar 

  • Elisma F, Jumarie C (2001) Evidence for cadmium uptake through Nramp2: metal speciation studies with Caco-2 cells. Biochem Biophys Res Commun 285:662–668

    Article  CAS  Google Scholar 

  • Fleming MD, Andrews NC (1998) Mammalian iron transport: an unexpected link between metal homeostasis and host defense. J Lab Clin Med 132:464–468

    Article  CAS  Google Scholar 

  • Garrick MD, Singleton ST, Vargas F, Kuo HC, Zhao L, KNÖPFEL M, Davidson T, Costa M, Paradkar P, Roth JA, Garrick LM (2006) DMT1: which metals does it transport? Biol Res 39:79–85

    Article  CAS  Google Scholar 

  • Georgieff MK, Wobken JK, Welle J, Burdo JR, Connor JR (2000) Identification and localization of divalent metal transporter-1 (DMT-1) in term human placenta. Placenta 21:799–804

    Article  CAS  Google Scholar 

  • Godt J, Scheidig F, Grosse-Siestrup C, Esche V, Brandenburg P, Reich A, Groneberg DA (2006) The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol 1:22

    Article  Google Scholar 

  • Goyer RA, Cherian MG (1992) Role of metallothionein in human placenta and rats exposed to cadmium. IARC Sci Publ 118:239–247

    CAS  Google Scholar 

  • Griffiths WJH, Kelly AL, Smith SJ, Cox TM (2000) Localization of iron transport and regulatory proteins in human cells. QJM 93:575–587

    Article  CAS  Google Scholar 

  • Gu C, Chen S, Xu X, Zheng L, Li Y, Wu K, Liu J, Qi Z, Han D, Chen G, Huo X (2009) Lead and cadmium synergistically enhance the expression of divalent metal transporter 1 protein in central nervous system of developing rats. Neurochem Res 34:1150–1156

    Article  CAS  Google Scholar 

  • Gundacker C, Hengstschläger M (2012) The role of the placenta in fetal exposure to heavy metals. Wien Med Wochenschr 162:201–206

    Article  Google Scholar 

  • Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    Article  CAS  Google Scholar 

  • Ishii T, Wallace AM, Zhang X, Gosselink J, Abboud RT, English JC, Pare PD, Sandford AJ (2006) Stability of housekeeping genes in alveolar macrophages from COPD patients. Eur Respir J 27:300–306

    Article  CAS  Google Scholar 

  • Järup L, Berglund M, Elinder CG, Nordberg G, Vanter M (1998) Health effects of cadmium exposure–a review of the literature and a risk estimate. Scand J Work Environ Health 24:1–51

    Article  Google Scholar 

  • Kim DW, Kim KY, Choi BS, Youn P, Ryu DY, Klaassen CD, Park JD (2007) Regulation of metal transporters by dietary iron, and the relationship between body iron levels and cadmium uptake. Arch Toxicol 81:327–334

    Article  CAS  Google Scholar 

  • Kuhnert BR, Kuhnert PM, Debanne S, Williams TG (1987) The relationship between cadmium zinc and birth weight in pregnant women who smoke. Am J Obstet Gynecol 157:1247–1251

    Article  CAS  Google Scholar 

  • Lee PL, Gelbart T, West C, Halloran C, Beutler E (1998) The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cell Mol Dis 24:199–215

    Article  CAS  Google Scholar 

  • Martelli A, Rousselet E, Dycke C, Bouron A, Moulis JM (2006) Cadmium toxicity in animal cells by interference with essential metals. Biochimie 88:1807–1814

    Article  CAS  Google Scholar 

  • McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5:299–309

    Article  CAS  Google Scholar 

  • Nishijo M, Satarug S, Honda R, Tsuritani I, Aoshima K (2004) The gender differences in health effects of environmental cadmium exposure and potential mechanisms. Mol Cell Biochem 255:87–92

    Article  CAS  Google Scholar 

  • Osman K, Åkesson A, Berglund M, Bremme K, Schütz A, Ask K, Vahter M (2000) Toxic and essential elements in placentas of Swedish women. Clin Biochem 33:131–138

    Article  CAS  Google Scholar 

  • Phuapittayalert L, Norkaew T, Supanpaiboon W, Chuenchoojit S, Hipkeao W, Swaddiwudhipong W, Sakulsak N (2013) Increasing of syncytial knot and fibrinoid deposit in high-cd accumulated human placentas. Int J Morphol 31:1210–1215

    Article  Google Scholar 

  • Phuapittayalert L, Saenganantakarn P, Supanpaiboon W, Cheunchoojit S, Hipkaeo W, Sakulsak N (2016) Increasing CACNA1C expression in placenta containing high cd level: an implication of cd toxicity. Environ Sci Pollut Res 23:24592–24600

    Article  CAS  Google Scholar 

  • Piasek M, Blanuša M, Kostial K, Laskey JW (2001) Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol 15:673–681

    Article  CAS  Google Scholar 

  • Roggi C, Sabbioni E, Minoia C, Ronchi A, Gatti A, Hansen B, Silva S, Maccarini L (1995) Trace element reference values in tissues from inhabitants of the European Union. IX. Harmonization of statistical treatment: blood cadmium in Italian subjects. Sci Total Environ 166:235–243

    Article  CAS  Google Scholar 

  • Rolfs A, Bonkovsky HL, Kohlroser JG, McNeal K, Sharma A, Berger UV, Hediger MA (2002) Intestinal expression of genes involved in iron absorption in humans. Am J Physiol Gastrointest Liver Physiol 282:G598–G607

    Article  CAS  Google Scholar 

  • Ryu DY, Lee SJ, Park DW, Choi BS, Klaassen CD, Park JD (2004) Dietary iron regulates intestinal cadmium absorption through iron transporters in rats. Toxicol Lett 152:19–25

    Article  CAS  Google Scholar 

  • Simmons R, Sukreeyapongse O, Noble A, Chinabut N (2005a) Report of LDD-IWMI land zoning and Cd risk assessment activities undertaken in Phatat Pha Daeng and Mae Tao Mai sub-districts, Mae Sot, Tak Province, Thailand. Final report. Bangkok, Thailand: International Water Management Institute (IWMI), SEA Regional Office; Bangkok, Thailand: Land Development Department. http://cpspace.cgiar.org/handle/10568/39660. Accessed 06 July 2018

  • Simmons RW, Pongsakul P, Saiyasitpanich D, Klinphoklap S (2005b) Elevated levels of cadmium and zinc in paddy soils and elevated levels of cadmium in rice grain downstream of a zinc mineralized area in Thailand: implications for public health. Environ Geochem Health 27:501–511

    Article  CAS  Google Scholar 

  • Suzuki T, Momoi K, Hosoyamada M, Kimura M, Shibasaki T (2008) Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo. Toxicol Appl Pharmacol 227:462–467

    Article  CAS  Google Scholar 

  • Swaddiwudhipong W, Limpatanachote P, Mahasakpan P, Krintratun S, Padungtod C (2007) Cadmium-exposed population in Mae Sot District, Tak Province: 1. Prevalence of high urinary cadmium levels in the adults. Medical. J Med Assoc Thail 90:143–148

    Google Scholar 

  • Tallkvist J, Bowlus CL, Lönnerdal B (2001) DMT1 gene expression and cadmium absorption in human absorptive enterocytes. Toxicol Lett 122:171–177

    Article  CAS  Google Scholar 

  • Tian LL, Zhao YC, Wang XC, Gu JL, Sun ZJ, Zhang YL, Wang JX (2009) Effects of gestational cadmium exposure on pregnancy outcome and development in the offspring at age 4.5 years. Biol Trace Elem Res 132:51–59

    Article  CAS  Google Scholar 

  • Vahter M, Åkesson A, Lidén C, Ceccatelli S, Berglund M (2007) Gender differences in the disposition and toxicity of metals. Environ Res 104:85–95

    Article  CAS  Google Scholar 

  • World Health Organization (2000) Chapter 6.3 cadmium: air quality guidelines-2nd edition. Denmark: WHO regional office for Europe. http://www.euro.who.int/__data/assets/pdf_file/0016/123073/AQG2ndEd_6_3cadmium.pdf. Accessed 06 July 2018

  • Wu X, Jin T, Wang Z, Ye T, Kong Q, Nordberg G (2001) Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium. J Occup Environ Med 43:898–904

    Article  CAS  Google Scholar 

  • Zadorozhnaja TD, Little RE, Miller RK, Mendel NA, Taylor RJ, Presley BJ, Gladen BC (2000) Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine. J Toxicol Environ Health A 61:255–263

    Article  CAS  Google Scholar 

  • Zhang B, Georgiev O, Hagmann M, Günes Ç, Cramer M, Faller P, Vasák M, Schaffner W (2003) Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein. Mol Cell Biol 23:8471–8485

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would especially like to thank all Dr. Witaya Swaddiwudhipong and hospital staffs of Mae Sot General Hospital for research collaboration and sample collection. We are sincerely grateful to Dr. Roger Timothy Callaghan, Mae Fah Lung University for assistance with proof reading. We gratefully express our sincere thanks to Associate Professor Dr. Wattana Weerachatyanukul and his research team (SK, LP and NT) at Faculty of Science, Mahidol University for initiating the Western blot analysis and useful suggestion. Finally, we would like to thank the Faculty of Medical Science, Naresuan University for all facilities provision.

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This research is financially supported by the Thailand Research Fund (TRF).

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Correspondence to Natthiya Sakulsak.

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All procedures were approved by the Human Ethics Committee of Naresuan University, Thailand (Project No. 50-03-01-0017). All participants gave informed consent to participate in this study.

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Responsible editor: Philippe Garrigues

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Somsuan, K., Phuapittayalert, L., Srithongchai, Y. et al. Increased DMT-1 expression in placentas of women living in high-Cd-contaminated areas of Thailand. Environ Sci Pollut Res 26, 141–151 (2019). https://doi.org/10.1007/s11356-018-3598-2

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