Intergenerational and transgenerational effects of endocrine-disrupting chemicals in the offspring brain development and behavior
Open accessAbstract
Endocrine-disrupting chemicals (EDCs) are a group of substances that can alter normal body functioning by disrupting the various patterns of hormone secretion and action. Some of these substances are used as plasticizers (e.g., bisphenols and phthalates) and agrochemicals (e.g., vinclozolin). EDC exposure can occur by many routes, including oral by contaminated food and water, through the skin, inhalation, and by placental transfer from mother to fetus or mother to infant (via lactation). The increase in EDCs used by the industry has strongly impacted our health. An increasing number of scientific works have reported the effects of EDCs on cancer development, metabolism, heart disease, and fertility. Most recently, studies on EDCs effects on behavior and the developing brain are raising major concerns related to the formation of sex differences and to the increased prevalence of neuropsychiatric disorders. In this review, we highlight the recent findings of the effects of pre-, peri-, and postnatal exposure to the three well-studied EDCs (i.e., bisphenols (BPA, BPS, BPF, and BPAF), phthalates (DBP, BBP, DEHP, and DiPeP), and vinclozolin (VIN)) on developing brain and behavior across generations in experimental animals.
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Regulatory measures have led to a partial decline in BPA use, and structurally related substitutes such as BPS, BPF, and BPAF have been increasingly introduced.
“Although regulatory measures in recent years have led to a partial decline in BPA use, structurally related substitutes such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) have been increasingly introduced (Dias et al., 2025).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dias et al., 2025
In the “Bisphenols exposure” section (page unavailable), the paper identifies BPF as a structurally related substitute for BPA, BPS as an analog, and BPAF as a new structurally related chemical. It notes a lowered European BPA intake limit, but does not say regulatory measures caused BPA use to decline or that use of all three alternatives has increased. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFemale offspring of the third generation (F3) exhibited reduced anxiety after ancestral high-dose DEHP exposure, whereas no such effect was observed in males; this sex-specific difference correlated with reduced ERα expression in the amygdala of F3 females.
“A related study showed that female offspring of the third generation (F3) exhibited reduced anxiety after ancestral high-dose DEHP exposure, whereas no such effect was observed in males; this sex-specific difference correlated with reduced ERα expression in the amygdala of F3 females (Dias et al., 2025).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dias et al., 2025
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Experimental — accuracy not yet measuredIncreased phthalate exposure has been associated with neurocognitive problems in later childhood.
“Increased phthalate exposure has further been associated with neurocognitive problems in later childhood (Bettio et al., 2020; Dias et al., 2025).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dias et al., 2025
The ‘Intergenerational effects of EDCs > Phthalates exposure’ section reports learning and memory deficiencies after perinatal phthalate exposure in rodent offspring and says exposure can affect animal cognition. It does not establish the claimed association with neurocognitive problems in later childhood in humans. (LLM, conf=0.84)
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- Authors
- Dias, G. R. M., Giusti, F. C. V., de Novais, C. O., de Oliveira, M. A. L., Paiva, A. G., Kalil-Cutti, B., Mahoney, M. M., & Graceli, J. B.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- University of Illinois System (US)
- Southern Illinois University Carbondale (US)
- Corresponding author
- Graceli, Jones Bernardes
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2025-05-21
- Volume
- 16
- Pages
- 1571689-1571689
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC12133532
- OpenAlex
- W4410528341
- Cited by
- 14
- References
- 138
- Citations by year
- 2026: 11 · 2025: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (03 2021, 2018‐4, 307224/2021-0, 311709/2018–4, 19/2022, 429035/2018–7, 311709/2018)
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (19/2022, E-26/, E-26/210)
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais (03346–18, 311709/2018-4)
- Fundação de Amparo à Pesquisa e Inovação do Espírito Santo (03/2021, #572/2018, 981/2022)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- endocrine disruptors, intergenerational effects, transgenerational effects, offspring neurodevelopment, behavior, bisphenols, phthalates, vinclozolin, prenatal exposure, placental transfer, lactation, sex differences, neuropsychiatric disorders, developmental neurotoxicity
- MeSH terms
- Animals, Behavior, Benzhydryl Compounds, Brain, Female, Humans, Phenols, Phthalic Acids, Pregnancy, Prenatal Exposure Delayed Effects, Endocrine Disruptors
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