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Cited by 94Sexual Differentiation and DisordersEffects and risks of endocrine disrupting chemicalsEpigenetics and DNA Methylation

Epigenetic impacts of endocrine disruptors in the brain

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Walker, Deena M., Gore, Andrea C.·2017·Frontiers in Neuroendocrinology
DOI 10.1016/j.yfrne.2016.09.002PMC PMC5429819
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Abstract

The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner.

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Crossref · 10.1016/j.yfrne.2016.09.002

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  • Exposure to BPA and BPS in zebrafish led to premature hypothalamic neurogenesis even at low doses.

    “In experimental studies, exposure to BPA and BPS in zebrafish led to premature hypothalamic neurogenesis even at low doses (Kinch et al., 2015; Walker and Gore, 2017).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Walker and Gore, 2017

    The claim appears in the title of Kinch et al. (2015) in the References (page unavailable), but Walker and Gore do not report the zebrafish neurogenesis finding in the passages retrieved. Section 2.3 cites Kinch et al. for BPA's effects on hormone systems instead. The specific low-dose BPA/BPS neurogenesis claim is credited to Kinch et al., not reported by this review. (LLM, conf=0.83) It matches “Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish” (2015) instead.

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  • EDC-induced disturbances of receptor signaling, calcium homeostasis, oxidative balance, and gene regulation can have persistent consequences for neural plasticity, cognition, and behavior.

    “Because exposure frequently occurs during highly sensitive developmental windows, including fetal life and early childhood, EDC-induced disturbances of receptor signaling, calcium homeostasis, oxidative balance, and gene regulation can have persistent consequences for neural plasticity, cognition, and behavior (Parent et al., 2011; Schug et al., 2015; Walker and Gore, 2017; Weiss, 2007).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Walker and Gore, 2017

    Section 1.1 says fetuses, infants, and children are especially vulnerable to EDC exposure and that effects may appear later; it also describes interference with hormone receptors. Sections 1.3 and 5.2 discuss enduring changes in brain organization, gene regulation, and behavior. The passages do not establish calcium-homeostasis or oxidative-balance disturbances, or the claimed consequences for cognition; section 1.2 discusses neural plasticity primarily in relation to hormones rather than demonstrating that EDCs alter it. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • PCBs accumulate in the fatty tissue of animals and humans and bioaccumulate in the food chain, leading to continuous exposure.

    “They accumulate in the fatty tissue of animals and humans and bioaccumulate in the food chain, leading to continuous exposure (Parent et al., 2011; Schug et al., 2015; Walker and Gore, 2017).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Walker and Gore, 2017

    Section 2.3.2 (page unavailable) says PCBs are stable, lipophilic compounds that persist in the environment and bioaccumulate up the food chain. It does not specifically say they accumulate in the fatty tissue of animals and humans or that this leads to continuous exposure. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Walker, D. M., & Gore, A. C.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • The University of Texas at Austin (US)
Corresponding author
Walker, Deena M.
ORCID
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2017-01
Volume
44
Pages
1-26
ISSN
0091-3022 (ISSN-L)
DOI
10.1016/j.yfrne.2016.09.002
PMC
PMC5429819
OpenAlex
W2522814857
Cited by
94
References
27
Citations by year
2026: 12 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 13 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 7
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Frontiers in Neuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
endocrine disruptors, epigenetics, DNA methylation, sexual differentiation of the brain, hypothalamus, sex hormone receptors, perinatal exposure, histone modifications, non-coding RNA, sex differences, reproductive behavior
MeSH terms
Animals, Female, Humans, Male, Reproduction, RNA, Sex Characteristics, Epigenesis, Genetic, Endocrine Disruptors, Epigenomics

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