Skip to main content
SpringerLink
Log in

Partition of metals in the maternal/fetal unit and lead-associated decreases of fetal iron and manganese: an observational biomonitoring approach

  • Reproductive Toxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

To systematically study the partition of environmental metals including lead, mercury, and cadmium and essential minerals such as iron, manganese, copper, and zinc in the maternal/fetal unit of healthy pregnant women, we analyzed blood and umbilical cord blood samples of 50 healthy mother/child pairs using a biomonitoring approach. The levels of essential minerals in healthy pregnant women were significantly different from those of the general population. The partition of essential minerals and environmental metals and their associations between maternal and umbilical cord blood were metal-specific. Lead entered the fetal environment nearly unaffected. The median fetal level was only 10 % lower than the corresponding maternal concentration (10.3 vs. 11.5 μg/l, P = 0.0038). Mercury accumulated in the fetal unit resulting in more than a threefold increase in fetal compared to maternal exposure (1.48 vs. 0.44 μg/l, P < 0.0001). In contrast, placental transfer of Cd was limited, and median fetal exposure was <0.1 μg/L. We finally used the data to assess the influence of exposures to environmental metals on fetal homeostasis of essential minerals because environmental metals such as lead are capable of interfering with normal cellular functions of essential minerals by mimicking their pathways. A subtle but systematic and dose-dependent effect of environmental exposure to lead on fetal homeostasis of manganese and iron in terms of reducing their concentrations in the fetal unit was found (P ≤ 0.039). The observed associations remained unaffected in the presence of mercury and cadmium. The results illustrate the need to establish specific normative levels of essential minerals in pregnant women. Additionally, the study provides initial insights into the mode-of-action of lead in the fetus at current environmental exposures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ashworth CJ, Antipatis C (2001) Micronutrient programming of development throughout gestation. Reproduction 122:527–535

    Article  PubMed  CAS  Google Scholar 

  • ATSDR (1999) Toxicological profile for mercury. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • ATSDR (2004) Toxicological profile for copper. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • ATSDR (2005) Toxicological profile for zinc. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • ATSDR (2007) Toxicological profile for lead. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • ATSDR (2008a) Toxicological profile for manganese. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • ATSDR (2008b) Toxicological profile for cadmium. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • Ballatori N (2002) Transport of toxic metals by molecular mimicry. Environ Health Perspect 110(S5):689–694

    Article  PubMed  CAS  Google Scholar 

  • Barceloux DG (1999) Manganese. J Toxicol Clin Toxicol 37:293–307

  • Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, Seifert B (2002) German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int J Hyg Environ Health 205:297–308

    Article  PubMed  Google Scholar 

  • Bellinger DC (2008a) Very low lead exposures and children’s neurodevelopment. Curr Opin Pediatr 20:172–177

    Article  PubMed  Google Scholar 

  • Bellinger DC (2008b) Lead neurotoxicity and socioeconomic status: conceptual and analytical issues. Neurotoxicology 29:828–832

    Article  PubMed  CAS  Google Scholar 

  • BfR (2008) Consumer tip for pregnant and breastfeeding women to restrict their consumption of tuna fish is still valid [in German]. Statement 041/2008, Federal Institute for Risk Assessment, Berlin, Germany

  • Björnberg KA, Vahter M, Petersson-Grawé K, Glynn A, Cnattingius S, Darnerud PO, Atuma S, Aune M, Becker W, Berglund M (2003) Methyl mercury and inorganic mercury in Swedish pregnant women and in cord blood: influence of fish consumption. Environ Health Perspect 111:637–641

    Article  PubMed  Google Scholar 

  • Björnberg KA, Vahter M, Berglund B, Niklasson B, Blennow M, Sandborgh-Englund G (2005) Transport of methylmercury and inorganic mercury to the fetus and breast-fed infant. Environ Health Perspect 113:1381–1385

    Article  PubMed  Google Scholar 

  • Blomgren K, Hagberg H (2006) Free radicals, mitochondria, and hypoxia-ischemia in the developing brain. Free Radic Biol Med 40:388–397

    Article  PubMed  CAS  Google Scholar 

  • Bloomingdale A, Guthrie LB, Price S, Wright RO, Platek D, Haines J, Oken E (2010) A qualitative study of fish consumption during pregnancy. Am J Clin Nutr 92:1234–1240

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Hengstler JG (2008) Aluminium and lead toxicity revisited: mechanisms explaining the particular sensitivity of the brain to oxidative damage. Arch Toxicol 82:787–788

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Marchan R (2010) Iron dysregulation: an important aspect in toxicology. Arch Toxicol 84:823–824

    Article  PubMed  CAS  Google Scholar 

  • Buonocore G, Perrone S, Bracci R (2001) Free radicals and brain damage in the newborn. Biol Neonate 79:180–186

    Article  PubMed  CAS  Google Scholar 

  • CDC (2009) 4th National Report on human exposure to environmental chemicals. Centers for Disease Control and Prevention. US Department of Health and Human Services, Atlanta, GA. http://www.cdc.gov/exposurereport

  • Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2011) Zinc and human health: an update. Arch Toxicol 86:521–534

    Article  PubMed  Google Scholar 

  • Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH (2008) Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 26:960–968

    Article  PubMed  CAS  Google Scholar 

  • Clarkson TW (1987) Metal toxicity in the central nervous system. Environ Health Perspect 75:59–64

    Article  PubMed  CAS  Google Scholar 

  • Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD (2000) Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol 279:G767–G774

    PubMed  CAS  Google Scholar 

  • Crump KS, Kjellström T, Shipp AM, Silvers A, Stewart A (1998) Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal 18:701–713

    Article  PubMed  CAS  Google Scholar 

  • Davidson PW, Myers GJ, Cox C, Wilding GE, Shamlaye CF, Huang LS, Cernichiari E, Sloane-Reeves J, Palumbo D, Clarkson TW (2006) Methylmercury and neurodevelopment: longitudinal analysis of the Seychelles child development cohort. Neurotoxicol Teratol 28:529–535

    Article  PubMed  CAS  Google Scholar 

  • Davidson PW, Leste A, Benstrong E, Burns CM, Valentin J, Sloane-Reeves J, Huang LS, Miller WA, Gunzler D, van Wijngaarden E, Watson GE, Zareba G, Shamlaye CF, Myers GJ (2010) Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study. Neurotoxicology 31:439–447

    Article  PubMed  CAS  Google Scholar 

  • Debes F, Budtz-Jørgensen E, Weihe P, White RF, Grandjean P (2006) Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol 28:363–375

    Article  PubMed  CAS  Google Scholar 

  • Franklin RB, Costello LC (2009) The important role of the apoptotic effects of zinc in the development of cancers. J Cell Biochem 106:750–757

    Article  PubMed  CAS  Google Scholar 

  • Grandjean P (2010) Even low-dose lead exposure is hazardous. Lancet 376:855–856

    Article  PubMed  Google Scholar 

  • Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, Murata K, Sørensen N, Dahl R, Jørgensen PJ (1997) Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 19:417–428

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hansen S, Nieboer E, Sandanger TM, Wilsgaard T, Thomassen Y, Veyhe AS, Odland JØ (2011) Changes in maternal blood concentrations of selected essential and toxic elements during and after pregnancy. J Environ Monit 13:2143–2152

    Article  PubMed  CAS  Google Scholar 

  • Harville EW, Hertz-Picciotto I, Schramm M, Watt-Morse M, Chantala K, Osterloh J, Parsons PJ, Rogan W (2005) Factors influencing the difference between maternal and cord blood lead. Occup Environ Med 62:263–269

    Article  PubMed  CAS  Google Scholar 

  • Ikonomidou C, Kaindl AM (2011) Neuronal Death and Oxidative Stress in the Developing Brain. Antioxid Redox Signal 14:1535–1550

    Article  PubMed  CAS  Google Scholar 

  • Iyengar GV (1987) Reference values for the concentrations of As, Cd, Co, Cr, Fe, I, Hg, Mn, Mo, Ni, Pb, Se, and Zn in selected human tissues and body fluids. Biol Trace Element Res 12:263–295

    Article  CAS  Google Scholar 

  • Jones EA, Wright JM, Rice G, Buckley BT, Magsumbol MS, Barr DB, Williams BL (2010) Metal exposures in an inner-city neonatal population. Environ Int 36:649–654

    Article  PubMed  CAS  Google Scholar 

  • Kell DB (2010) Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 84:825–889

    Article  PubMed  CAS  Google Scholar 

  • Kuhnert PM, Kuhnert BR, Erhard P, Brashear WT, Groh-Wargo SL, Webster S (1987) The effect of smoking on placental and fetal zinc status. Am J Obstet Gynecol 157:1241–1246

    PubMed  CAS  Google Scholar 

  • Lin CM, Doyle P, Wang D, Hwang YH, Chen PC (2010) The role of essential metals in the placental transfer of lead from mother to child. Reprod Toxicol 29:443–446

    Google Scholar 

  • Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: implications in disease. Free Radic Biol Med 47:344–356

    Article  PubMed  CAS  Google Scholar 

  • Moreno MA, Marin C, Vinagre F, Ostapczuk P (1999) Trace element levels in whole blood samples from residents of the city Badajoz, Spain. Sci Total Environ 229:209–215

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (NRC) (2000) Toxicological Effects of Methylmercury. National Academy Press, Washington, DC

    Google Scholar 

  • Ong CN, Chia SE, Foo SC, Ong HY, Tsakok M, Liouw P (1993) Concentrations of heavy metals in maternal and umbilical cord blood. Biometals 6:61–66

    Article  PubMed  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  PubMed  CAS  Google Scholar 

  • Röllin HB, Rudge CV, Thomassen Y, Mathee A, Odland JØ (2009) Levels of toxic and essential metals in maternal and umbilical cord blood from selected areas of South Africa—results of a pilot study. J Environ Monit 11:618–627

    Article  PubMed  Google Scholar 

  • Rudge CV, Röllin HB, Nogueira CM, Thomassen Y, Rudge MC, Odland JØ (2009) The placenta as a barrier for toxic and essential elements in paired maternal and cord blood samples of South African delivering women. J Environ Monit 11:1322–1330

    Article  PubMed  CAS  Google Scholar 

  • Schaller KH, Angerer J, Drexler H (2002) Quality assurance of biological monitoring in occupational and environmental medicine. J Chromatogr B 778:403–417

    Article  CAS  Google Scholar 

  • Schauder A, Avital A, Malik Z (2010) Regulation and gene expression of heme synthesis under heavy metal exposure—review. J Environ Pathol Toxicol Oncol 29:137–158

    Article  PubMed  CAS  Google Scholar 

  • Sexton K, Needham LL, Pirkle JL (2004) Human biomonitoring of environmental chemicals. Am Sci 92:38–45

    Google Scholar 

  • Spencer A (1999) Whole blood manganese levels in pregnancy and the neonate. Nutrition 15:731–734

    Article  PubMed  CAS  Google Scholar 

  • Takser L, Mergler D, de Grosbois S, Smargiassi A, Lafond J (2004) Blood manganese content at birth and cord serum prolactin levels. Neurotoxicol Teratol 26:811–815

    Google Scholar 

  • Thiel G, Cibelli G (2002) Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol 193:287–292

    Article  PubMed  CAS  Google Scholar 

  • Verstraeten SV, Aimo L, Oteiza P (2008) Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol 82:789–802

    Article  PubMed  CAS  Google Scholar 

  • WHO (1990) Methylmercury. Environ Health Crit 101, International Programme on Chemical Safety, World Health Organization, Geneva

  • Wood RJ (2009) Manganese and birth outcome. Nutr Rev 67:416–420

    Article  PubMed  Google Scholar 

  • Woodruff TJ, Zota AR, Schwartz JM (2011) Environmental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ Health Perspect 119:878–885

    Article  PubMed  Google Scholar 

  • Wright RO, Baccarelli A (2007) Metals and neurotoxicology. J Nutr 137:2809–2813

    PubMed  CAS  Google Scholar 

  • Yorifuji T, Debes F, Weihe P, Grandjean P (2011) Prenatal exposure to lead and cognitive deficit in 7- and 14-year-old children in the presence of concomitant exposure to similar molar concentration of methylmercury. Neurotoxicol Teratol 33:205–211

    Article  PubMed  CAS  Google Scholar 

  • Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO (2009) Maternal blood manganese levels and infant birth weight. Epidemiology 20:367–373

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded by the German Social Accident Insurance (DGUV) as part of their intramural research program. The content and the opinions of this article are solely the responsibility of the authors and do not necessarily represent the official views of DGUV. The authors gratefully acknowledge Eleonore Gutwinski for technical assistance and Dr. Rosemarie Marchan for editorial review of the manuscript prior submission.

Conflict of interest

The authors have no conflicts of interest.

Author information

Author notes

  1. Michael Kumbartski

    Present address: Department of Gynecology and Obstetrics, Ecclesiastical Hospital “Foundation Kreuznacher Diakonie”, Ringstraße 64, 55543, Bad Kreuznach, Germany

  2. Volker Harth

    Present address: Faculty of Medicine, Institute and Outpatient Clinic of Occupational Medicine, Saarland University Medical Center, Saarland University, 66421, Homburg, Germany

Authors and Affiliations

  1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr University Bochum, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany

    Ricarda S. Kopp, Volker Harth, Thomas Brüning & Heiko U. Käfferlein

  2. Department of Obstetrics and Gynecology, St. Josef and St. Elisabeth-Hospital, Ruhr University Bochum, Bleichstrasse 15, 44787, Bochum, Germany

    Michael Kumbartski

Authors
  1. Ricarda S. Kopp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Kumbartski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Volker Harth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Brüning
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heiko U. Käfferlein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heiko U. Käfferlein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kopp, R.S., Kumbartski, M., Harth, V. et al. Partition of metals in the maternal/fetal unit and lead-associated decreases of fetal iron and manganese: an observational biomonitoring approach. Arch Toxicol 86, 1571–1581 (2012). https://doi.org/10.1007/s00204-012-0869-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-012-0869-4

Keywords

Search

Navigation