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Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children

Journal of Exposure Science & Environmental Epidemiology volume 33, pages 865–873 (2023)Cite this article

Abstract

Background

Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated.

Methods

Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone.

Results

The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (β = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures.

Significance

Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels.

Impact statement

  • Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children’s health in e-waste areas are needed.

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Fig. 1: Overall combined effects of lead (Pb), cadmium (Cd), and mercury (Hg) on testosterone, androstenedione (A-dione), progesterone, and dehydroepiandrosterone (DHEA) (estimates and 95% confidence intervals).
Fig. 2: Single-exposure effects of lead (Pb), cadmium (Cd), and mercury (Hg) on testosterone, androstenedione (A-dione), progesterone, and dehydroepiandrosterone (DHEA).
Fig. 3: Univariate exposure-response plots for each heavy metal and testosterone, androstenedione (A-dione), progesterone, and dehydroepiandrosterone (DHEA).
Fig. 4: Bivariate exposure-response plots for two heavy metals and dehydroepiandrosterone (DHEA).

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

References

  1. Ackah M. Informal E-waste recycling in developing countries: Review of metal(loid)s pollution, environmental impacts and transport pathways. Environ Sci Pollut Res. 2017;24:24092–101.

    Article  Google Scholar 

  2. Baldé CP, Forti V, Gray V, Kuehr R, Stegmann P. The Global E-waste Monitor – 2017, United Nations University (UNU), International Telecommunication Union (ITU) & International Solid Waste Association (ISWA), Bonn/Geneva/Vienna. https://www.itu.int/dms_pub/itu-d/opb/gen/D-GEN-E_WASTE.01-2017-PDF-E.pdf.

  3. Forti V, Baldé CP, Kuehr R, Bel G. The Global E-waste Monitor 2020: Quantities, flows and the circular economy potential. United Nations University (UNU)/United Nations Institute for Training and Research (UNITAR) – co-hosted SCYCLE Programme, International Telecommunication Union (ITU) & International Solid Waste Association (ISWA), Bonn/Geneva/Rotterdam. https://www.itu.int/en/ITU-D/Environment/Pages/Spotlight/Global-Ewaste-Monitor-2020.aspx.

  4. Damrongsiri S, Vassanadumrongdee S, Tanwattana P. Heavy metal contamination characteristic of soil in WEEE (waste electrical and electronic equipment) dismantling community: a case study of Bangkok, Thailand. Environ Sci Pollut Res. 2016;23:17026–34.

    Article  CAS  Google Scholar 

  5. Ashrap P, Sánchez BN, Téllez-Rojo MM, Basu N, Tamayo-Ortiz M, Peterson KE, et al. In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City. Environ Res. 2019;177:108630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ren J, Cui J, Chen Q, Zhou N, Zhou Z, Zhang GH, et al. Low-level lead exposure is associated with aberrant sperm quality and reproductive hormone levels in Chinese male individuals: Results from the MARHCS study low-level lead exposure is associated with aberrant sperm quality. Chemosphere. 2020;224:125402.

    Article  Google Scholar 

  7. Gil F, Hernandez AF. Toxicological importance of human biomonitoring of metallic and metalloid elements in different biological samples. Food Chem Toxicol. 2015;80:287–97.

    Article  CAS  PubMed  Google Scholar 

  8. Park Y, Lee A, Choi K, Kim HJ, Lee JJ, Choi G, et al. Exposure to lead and mercury through breastfeeding during the first month of life: a CHECK cohort study. Sci Total Environ. 2018;612:876–83.

    Article  CAS  PubMed  Google Scholar 

  9. Alabi OA, Adeoluwa YM, Huo X, Xu X, Bakare AA. Environmental contamination and public health effects of electronic waste: an overview. J Environ Health Sci Eng. 2021;19:1209–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. LaKind JS, Wilkins AA, Berlin CM. Environmental chemicals in human milk: a review of levels, infant exposures and health, and guidance for future research. Toxicol Appl Pharm. 2004;198:184–208.

    Article  CAS  Google Scholar 

  11. Landrigan PJ, Sonawane B, Mattison D, E McCally M, Garg A. Chemical contaminants in breast milk and their impacts on children’s health: an overview. Environ Health Perspect. 2002;110:313–5.

    Article  Google Scholar 

  12. Lebbie TS, Moyebi OD, Asante KA, Fobil J, Brune-Drisse MN, Suk WA, et al. E-waste in Africa: a serious threat to the health of children. Int J Environ Res Public Health. 2021;18:8488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schoeman K, Bend JR, Hill J, Nash K, Koren G. Defining a lowest observable adverse effect hair concentrations of mercury for neurodevelopmental effects of prenatal methylmercury exposure through maternal fish consumption: a systematic review. Ther Drug Monit. 2009;31:670–82.

    Article  CAS  PubMed  Google Scholar 

  14. Dórea JG. Exposure to environmental neurotoxic substances and neurodevelopment in children from Latin America and the Caribbean. Environ Res. 2021;192:110199.

    Article  PubMed  Google Scholar 

  15. Dórea JG. Environmental exposure to low-level lead (Pb) co-occurring with other neurotoxicants in early life and neurodevelopment of children. Environ Res. 2019;177:108641.

    Article  PubMed  Google Scholar 

  16. Chan JKY, Xing GH, Xu Y, Liang Y, Chen LX, Wu SC, et al. Body loadings and health risk assessment of polychlorinated dibenzo-p-dioxins and dibenzofurans at an intensive electronic waste recycling site in China. Environ Sci Technol. 2007;41:7668–74.

    Article  CAS  PubMed  Google Scholar 

  17. Luo T, Hang JG, Nakayama SF, Jung CR, Ma CC, Kido T, et al. Dioxins in breast milk of Chinese mothers: a survey 40 years after the e-waste recycling activities. Sci Total Environ. 2021;758:143627.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Z, Hang JG, Feng H, Shi LL, Dong JJ, Shen B, et al. Effects of perinatal dioxin exposure on development of children: a three-year follow-up study of China cohort. Environ Sci Pollut Res. 2019;26:20780–6.

    Article  CAS  Google Scholar 

  19. Søeborg T, Frederiksen H, Mouritsen A, Johannsen TH, Main KM, Jørgensen N, et al. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults. Clin Chim Acta. 2014;437:6–13.

    Article  PubMed  Google Scholar 

  20. Yamashita K, Miyashiro Y, Maekubo H, Okuyama M, Honma S, Takahashi M, et al. Development of highly sensitive quantification method for testosterone and dihydrotestosterone in human serum and prostate tissue by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids. 2009;74:920–6.

    Article  CAS  PubMed  Google Scholar 

  21. Dong JJ, Ruan MC, Hang JG, Nakayama SF, Jung CR, Kido T, et al. The relationship between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children at an e-waste region in China. Int J Hyg Environ Health. 2020;229:113580.

    Article  CAS  PubMed  Google Scholar 

  22. Freire C, Amaya E, Gil F, Fernández MF, Murcia M, Llop S, et al. Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool children: The Environment and Childhood (INMA) Project. Sci Total Environ. 2018;621:340–51.

    Article  CAS  PubMed  Google Scholar 

  23. Guo J, Wu C, Zhang J, Qi X, Lv S, Jiang S, et al. Prenatal exposure to mixture of heavy metals, pesticides and phenols and IQ in children at 7 years of age: The SMBCS study. Environ Int. 2020;139:105692.

    Article  CAS  PubMed  Google Scholar 

  24. Bob JF, Valeri L, Henn BC, Christiani DC, Wright RO, Mazumdar M, et al. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics. 2015;16:493–508.

    Article  Google Scholar 

  25. Bobb JF. Package ‘bkmr’: Bayesian Kernel Machine Regression. https://cran.r-project.org/web/packages/bkmr/bkmr.pdf 2022. (accessed on 23 Oct 2022).

  26. Rosenfield RL. Normal and premature adrenarche. Endocr Rev. 2021;42:783–814.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Schnakenburg KV, Bidlingmaier F, Knorr D. 17-hydroxyprogesterone, androstenedione, and testosterone in normal children and in prepubertal patients with congenital adrenal hyperplasia. Eur J Pediatr. 1980;133:259–67.

    Article  Google Scholar 

  28. Sulcová J, Hill M, Hampl R, Stárka L. Age and sex related differences in serum levels of unconjugated dehydroepiandrosterone and its sulphate in normal subjects. J Endocrinol. 1997;154:57–62.

    Article  PubMed  Google Scholar 

  29. Kim JH, Lee YA, Lim YH, Lee K, Kim BN, Kim JI, et al. Changes in adrenal androgens and steroidogenic enzyme activities from ages 2, 4, to 6 years: a prospective cohort study. J Clin Endocrinol Metab. 2020;105:dgaa498.

    Article  PubMed  Google Scholar 

  30. Kumar U, Gaikwad V, Mayyas M, Bucknall M, Sahajwalla V. Application of high-resolution NMR and GC–MS to study hydrocarbon oils derived from noncatalytic thermal transformation of e-waste plastics. ACS Omega. 2018;3:9282–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fu J, Zhou Q, Liu J, Liu W, Wang T, Zhang Q, et al. High levels of heavy metals in rice (Oryza sativa L.) from a typical E-waste recycling area in southeast China and its potential risk to human health. Chemosphere. 2008;71:1269–75.

    Article  CAS  PubMed  Google Scholar 

  32. Gu W, Bai J, Yao H, Zhao J, Zhuang X, Huang Q, et al. Heavy metals in soil at a waste electrical and electronic equipment processing area in China. Waste Manag Res. 2017;35:1183–91.

    Article  CAS  PubMed  Google Scholar 

  33. Li X, Dong S, Su X. Copper and other heavy metals in grapes: a pilot study tracing influential factors and evaluating potential risks in China. Sci Rep. 2018;8:17407.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Yin H, Ma J, Li Z, Li Y, Meng T, Tang Z. Polybrominated diphenyl ethers and heavy metals in a regulated E-waste recycling site, eastern china: implications for risk management. Molecules. 2021;26:2169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Agusa T, Kunito T, Iwata H, Monirith I, Chamnan C, Tana TS, et al. Mercury in hair and blood from residents of Phnom Penh (Cambodia) and possible effect on serum hormone levels. Chemosphere. 2007;68:590–6.

    Article  CAS  PubMed  Google Scholar 

  36. Baraquoni NA, Qouta SR, Vänskä M, Diab SY, Punamäki RL, Manduca P. It takes time to unravel the ecology of war in Gaza, Palestine: long-term changes in maternal, newborn and toddlers’ heavy metal loads, and infant and toddler developmental milestones in the aftermath of the 2014 military attacks. Int J Environ Res Public Health. 2020;17:6698.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages. Hum Reprod Update. 1998;4:301–9.

    Article  CAS  PubMed  Google Scholar 

  38. Iavicoli I, Fontana L, Bergamaschi A. The effects of metals as endocrine disruptors. J Toxicol Environ Heal B. 2009;12:206–23.

    Article  CAS  Google Scholar 

  39. Li CJ, Yeh CY, Chen RY, Tzeng CR, Han BC, Chien LC. Biomonitoring of blood heavy metals and reproductive hormone level related to low semen quality. J Hazard Mater. 2015;300:815–22.

    Article  CAS  PubMed  Google Scholar 

  40. Waring RH, Harris RM. Endocrine disrupters: a human risk? Mol Cell Endocrinol. 2005;244:2–9.

    Article  CAS  PubMed  Google Scholar 

  41. Ji X, Li Z, Chen H, Li J, Tian H, Li Z, et al. Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals. Toxicology. 2015;334:22–32.

    Article  CAS  PubMed  Google Scholar 

  42. Kampalath RA, Jay JA. Sources of mercury exposure to children in low- and middle-income countries. J Health Pollut. 2015;5:33–51.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Louis GB, Faustman E, Hass U, Kavlock R, Sheldon L. Principles for evaluating health risks in children associated with exposure to chemicals. EHC. 2006;237:329.

    Google Scholar 

  44. Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108:511–33.

    PubMed  PubMed Central  Google Scholar 

  45. Ruggieri F, Majorani C, Domanico F, Alimonti A. Mercury in children: current state on exposure through human biomonitoring studies. Int J Environ Res Public Health. 2017;14:519.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Boucher O, Jacobson SW, Plusquellec P, Dewailly E, Ayotte P, Forget-Dubois N, et al. Prenatal methylmercury, postnatal lead exposure, and evidence of attention deficit/hyperactivity disorder among Inuit children in Arctic Quebec. Environ Health Perspect. 2012;120:1456–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Farzan SF, Howe CG, ChenY, Gilbert-Diamond D, Korrick S, Jackson BP, et al. Prenatal and postnatal mercury exposure and blood pressure in childhood. Environ Int. 2021;146:106201.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang M, Liu T, Wang G, Buckley JP, Guallar E, Hong X, et al. In utero exposure to heavy metals and trace elements and childhood blood pressure in a U.S. urban, low-Income, minority birth cohort. Environ Health Perspect. 2021;129:67005.

    Article  CAS  PubMed  Google Scholar 

  49. Modgil S, Lahiri DK, Sharma VL, Anand A. Role of early life exposure and environment on neurodegeneration: implications on brain disorders. Transl Neurodegener. 2014;3:9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Oliveira CS, Nogara PA, Ardisson-Araújo DMP, Aschner M, Rocha JBT, Dórea JG. Neurodevelopmental effects of mercury. Adv Neurotoxicol. 2018;2:27–86.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Tan SW, Meiller JC, Mahaffey KR. The endocrine effects of mercury in humans and wildlife. Crit Rev Toxicol. 2009;39:228–69.

    Article  CAS  PubMed  Google Scholar 

  52. Wang G, Tang WY, Ji H, Wang X. Prenatal exposure to mercury and precocious puberty: a prospective birth cohort study. Hum Reprod. 2020;36:712–20.

    Article  PubMed Central  Google Scholar 

  53. Nguyen TV, Wu M, Lew J, Albaugh MD, Botteron KN, Hudziak JJ, et al. Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development. Psychoneuroendocrinology. 2017;86:110–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mulligan EM, Hajcak G, Crisler S, Meyer A. Increased dehydroepiandrosterone (DHEA) is associated with anxiety in adolescent girls. Psychoneuroendocrinology. 2020;119:104751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kupsco A, Kioumourtzoglou MA, Just AC, Amarasiriwardena C, Estrada-Gutierrez G, Cantoral A, et al. Prenatal metal concentrations and childhood cardio-metabolic risk using Bayesian Kernel Machine Regression to assess mixture and interaction effects. Epidemiology. 2019;30:263–73.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Miklavčič A, Casetta A, Tratnik JS, Mazej D, Krsnik M, Mariuz M, et al. Mercury, arsenic and selenium exposure levels in relation to fish consumption in the Mediterranean area. Environ Res. 2013;120:7–17.

    Article  PubMed  Google Scholar 

  57. Barbone F, Rosolen V, Mariuz M, Parpinel M, Casetta A, Sammartano F, et al. Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: results from the Mediterranean PHIME cohort. Int J Hyg. Environ Health. 2019;222:9–21.

    CAS  Google Scholar 

  58. Vollset M, Iszatt N, Enger O, Gjengedal ELF, Eggesbo M. Concentration of mercury, cadmium, and lead in breast milk from Norwegian mothers: association with dietary habits, amalgam and other factors. Sci Total Environ. 2019;677:466–73.

    Article  CAS  PubMed  Google Scholar 

  59. Çebi A, Şengül Ü. Toxic metal and trace element status in the breast milk of Turkish new-born mothers. J Trace Elem Med Biol. 2022;74:127066.

    Article  PubMed  Google Scholar 

  60. Wang Y, Chen L, Gao Y, Zhang Y, Wang C, Zhou Y, et al. Effects of prenatal exposure to cadmium on neurodevelopment of infants in Shandong, China. Environ Pollut. 2016;211:67–73.

    Article  CAS  PubMed  Google Scholar 

  61. Lewis M, Worobey J, Ramsay DS, McCormack MK. Prenatal exposure to heavy metals: Effect on childhood cognitive skills and health status. Pediatrics 1992;89:1010–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the participants and their children participating in this study.

Funding

The work was supported by the Zhejiang Province Public Welfare Technology Application Research Project (CN) (grant numbers LGF22H260002; LGF21H300006; LGF18H260008; LGF20H170010), JSPS Grants-in-aid for Scientific Research (grant number JP19F19113) and the Jiaxing Science and Technology Bureau (CN) (grant number 2020AY30005).

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Authors and Affiliations

  1. School of Medicine, and Huzhou Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China

    Li Li Shi, Jianlin Lou & Xian Liang Sun

  2. School of Medicine, Jiaxing University, Jiaxing, China

    Li Li Shi, Jing Jian Dong, Hao Feng, Zheng Wang, Bin Shen & Xian Liang Sun

  3. Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China

    Jin Guo Hang

  4. Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Japan

    Shoji F. Nakayama & Chau-Ren Jung

  5. Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan

    Teruhiko Kido & Xian Liang Sun

  6. Cancer Control Center, Osaka International Cancer Institute, Osaka, Japan

    Chaochen Ma

  7. Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan

    Chau-Ren Jung

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Contributions

LLS and JGH Conceptualization, Methodology, Software, Formal analysis, Writing-original draft. JJD, HF, ZW, and BS Chemical analysis, Writing - review & editing. SFN, TK, and CM. Writing-review & editing. CRJ and XLS Conceptualization, Resources, Writing-review & editing, Supervision, Project administration, Funding acquisition.

Corresponding authors

Correspondence to Xian Liang Sun or Chau-Ren Jung.

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This study was approved by the ethics committee of the Affiliated Chinese Hospital of Jiaxing University.

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Shi, L.L., Hang, J.G., Lou, J. et al. Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children. J Expo Sci Environ Epidemiol 33, 865–873 (2023). https://doi.org/10.1038/s41370-023-00539-9

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