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Bisphenol A and its effects on the systemic organs of children

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Abstract

For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children’s health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.

Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans.

What is known:

• Very limited reviews are available on how BPA adversely affects children’s health.

• Previous papers mainly covered two systems in children.

What is new:

• Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives.

• Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.

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Abbreviations

AR:

Androgen receptor

AGD:

Anogenital distance

BMI:

Body mass index

BPA:

Bisphenol A

BPAF:

Bisphenol AF

BPF:

Bisphenol F

BPS:

Bisphenol S

CVD:

Cardiovascular disease

EDC:

Endocrine-disrupting chemical

EGFR:

Epidermal growth factor receptor

ER:

Oestrogen receptor

FXR:

Farnesoid X receptor

GnRH:

Gonadotropin-releasing hormone

GPER:

G-protein-coupled receptor

HPA:

Hypothalamic–pituitary–adrenal

HRV:

Heart rate variability

LOAEL:

Lowest observed adverse effect level

Maxi-K:

Large conductance calcium-activated channel

miRNA:

MicroRNA

PCOS:

Polycystic ovary syndrome

PND:

Postnatal day

SRC:

Steroid receptor coactivator

TR:

Thyroid receptor

TSH:

Thyroid-stimulating hormone

T2D:

Type 2 diabetes mellitus

VGSC:

Voltage-gated sodium channel

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Acknowledgements

The authors acknowledge the institutional support given by the Universiti Teknologi MARA (UiTM).

Funding

This review paper was funded by the Fundamental Research Grant Scheme from the Ministry of Higher Education, Malaysia, grant number 600-IRMI/FRGS 5/3(387/2019).

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Author notes

  1. Sarah Zulkifli and Amirah Abdul Rahman contributed equally to this work.

Authors and Affiliations

  1. Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, 47000, Sungai Buloh, Malaysia

    Sarah Zulkifli

  2. Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, 47000, Sungai Buloh, Malaysia

    Amirah Abdul Rahman & Siti Hamimah Sheikh Abdul Kadir

  3. Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, 47000, Sungai Buloh, Malaysia

    Siti Hamimah Sheikh Abdul Kadir & Noor Shafina Mohd Nor

  4. Department of Paediatrics, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, 47000, Sungai Buloh, Malaysia

    Noor Shafina Mohd Nor

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The manuscript was written and edited by Sarah Zulkifli and Amirah Abdul Rahman and conceptualised and edited by Siti Hamimah Sheikh Abdul Kadir and Noor Shafina Mohd Nor. All authors worked together in improving the manuscript and gave approval of the submitted and published versions.

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Correspondence to Noor Shafina Mohd Nor.

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Zulkifli, S., Rahman, A.A., Kadir, S.H.S.A. et al. Bisphenol A and its effects on the systemic organs of children. Eur J Pediatr 180, 3111–3127 (2021). https://doi.org/10.1007/s00431-021-04085-0

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