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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 (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).

Data availability

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

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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 (2023). https://doi.org/10.1038/s41370-023-00539-9

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  • DOI: https://doi.org/10.1038/s41370-023-00539-9

Keywords

  • Multiple heavy metals
  • Bayesian kernel machine regression
  • Prenatal exposure
  • E-waste
  • Mercury
  • DHEA

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