Nuclear hormone receptors control fundamental processes of human fetal neurodevelopment: Basis for endocrine disruption assessment

Environment International, Journal Year: 2025, Volume and Issue: 198, P. 109400 - 109400

Published: March 21, 2025

Despite growing awareness of endocrine disrupting chemicals (EDCs), knowledge gaps remain regarding their effects on human brain development. EDC risk assessment focuses primarily EATS modalities (estrogens, androgens, thyroid hormones, and steroidogenesis), overlooking the broader range hormone receptors expressed in developing brain. This limits evaluation for potential to cause disruption-mediated developmental neurotoxicity (ED-DNT). The Neurosphere Assay, an vitro test method (DNT) evaluation, is integral component DNT testing battery, which has been used screen a broad domain environmental chemicals. Here, we define endocrine-related applicability Assay by assessing impact specificity 14 seven key neurodevelopmental processes (KNDPs), neural progenitor cell (NPC) proliferation, migration radial glia, neurons, oligodendrocytes, neurite outgrowth, differentiation neurons oligodendrocytes. Comparative analyses rat NPCs both sexes revealed species- sex-specific responses. Mechanistic insights were obtained through RNA sequencing agonist/antagonist co-exposures. Most receptor agonists modulated KNDPs at concentrations physiologically relevant concentrations. Phenotypic induced glucocorticoid (GR), liver X (LXR), peroxisome proliferator-activated beta/delta (PPARβδ), retinoic acid (RAR) retinoid (RXR) activation counteracted antagonists, confirming specificity. Transcriptomics highlighted crosstalk involvement conserved pathways (e.g. Notch Wnt). Species comparisons identified limited concordance receptor-regulated between NPCs. study presents novel findings cellular molecular actions fetal NPCs, highlights major species differences, illustrates Assay's relevance detecting MoAs, supporting its application human-based ED-DNT assessment.

Language: Английский

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Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 920, P. 170754 - 170754

Published: Feb. 16, 2024

Language: Английский

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Bisphenol A (BPA) and neurological disorders: An overview

The International Journal of Biochemistry & Cell Biology, Journal Year: 2024, Volume and Issue: 173, P. 106614 - 106614

Published: June 28, 2024

Language: Английский

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Investigating the impact of endocrine-disrupting compounds on antepartum mental health at the Nexus of genetic insights and maternal-fetal outcomes: A prospective study

General Hospital Psychiatry, Journal Year: 2025, Volume and Issue: 94, P. 174 - 183

Published: March 13, 2025

Language: Английский

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Changing the structure of PFOA and PFOS: a chemical industry strategy or a solution to avoid thyroid-disrupting effects?

Journal of Endocrinological Investigation, Journal Year: 2024, Volume and Issue: 47(8), P. 1863 - 1879

Published: March 24, 2024

Abstract Background The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation persistence in the environment animals as well hazardous health effects. As a result, new congeners PFAS have rapidly replaced so-called “old long-chain PFAS” (mainly PFOA PFOS), currently out-of-law banned by most countries. These compounds derive from original structure PFAS”, cutting or making little conformational changes to structure, thus obtaining molecules with similar industrial applications. were designed obtain "safer" compounds. Indeed, old-long-chain reported exert thyroid disruptive effects vitro, vivo humans. However, shreds evidence accumulated so far indicate that “restyling” old leads production compounds, not only functionally previous ones but also potentially free adverse bioaccumulation. Studies aimed at characterizing new-PFAS on function some these showed Purpose present review is providing an overview recent data regarding novel alternatives function. Results conclusions An extensive current legislation obtained vitro studies evaluating exposure PFOS alternatives, mixture will be provided.

Language: Английский

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The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: April 11, 2024

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered growth, syncytialization, trophoblast invasion. However, no epidemiologic study reported exposure EDCs asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this was evaluate the association EDC FGR. This a prospective cohort including women admitted for delivery Maternal Fetal Center at Seoul St. Mary’s Hospital October 2021 2022. urine cord blood samples were collected, levels bisphenol-A (BPA), monoethyl phthalates, perfluorooctanoic acid in each specimen analyzed. We investigated linear non-linear parameters, head circumference (HC)/abdominal (AC) ratio as an parameter. compared fetuses with without Of EDCs, only BPA showed HC/AC after adjusting confounding variables ( β = 0.003, p < 0.05). When comparing normal FGR groups, group significantly higher maternal (maternal BPA, 3.99 μg/g creatinine vs. 1.71 [ 0.05]; 1.96 μg/L −0.86 0.05]). In conclusion, show patterns. High might be associated

Language: Английский

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Association between urinary phthalates and phthalate metabolites and cancer risk: A systematic review and meta-analysis

Heliyon, Journal Year: 2024, Volume and Issue: 10(8), P. e29684 - e29684

Published: April 1, 2024

Phthalates, widely utilized in industrial products, are classified as endocrine-disrupting chemicals (EDCs). Although certain phthalate and their metabolites have been implicated cancer development, the reported findings exhibited inconsistencies. Therefore, we conducted comprehensive literature search to assess association between risk by identifying original studies measuring phthalates or reporting correlation with until July 4, 2023. The Odds Ratios (ORs) corresponding 95% confidence intervals (CIs) were extracted analyzed estimate risk. Pooled data from eleven studies, including 3101 patients 6858 controls, using a fixed- random-effects model based on heterogeneity tests. When comparing extreme categories of different metabolites, observed significant urinary (MEHHP, MECPP, DBP MBzP) our meta-analysis reinforce existing evidence that is strongly associated development. Further investigations warranted elucidate underlying mechanisms this association. These results may offer novel insights into

Language: Английский

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A comprehensive review of medicinal plants and their beneficial roles in alleviating bisphenol A–induced organ toxicity

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

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Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 296, P. 118188 - 118188

Published: April 22, 2025

Language: Английский

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Associations between mycoestrogen exposure and sex steroid hormone concentrations in maternal serum and cord blood in the UPSIDE pregnancy cohort

International Journal of Hygiene and Environmental Health, Journal Year: 2024, Volume and Issue: 260, P. 114405 - 114405

Published: June 14, 2024

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN metabolites closely resembles 17β-estradiol (E2), they interact with estrogen receptors α/β earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts activity impairs fetal growth. Here, our objective was evaluate relationships between mycoestrogen sex steroid hormone concentrations maternal circulation cord blood for first time humans. each trimester, pregnant participants UPSIDE study (n = 297) provided urine analysis serum analysis. At birth, placental steroids were measured. We fitted longitudinal models examining log-transformed relation hormones, adjusting covariates. Secondarily, multivariable linear examined associations at point (1st, 2nd, 3rd trimesters, delivery). additionally considered effect modification by sex. its metabolite, α-zearalenol (α-ZOL), detected >93% >75% samples; >80% placentas had detectable mycoestrogens. Longitudinal from full cohort exhibited few significant associations. sex-stratified analyses, pregnancies male fetuses, estrone (E1) free testosterone (fT) inversely associated (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT -3.22 -5.68, -0.70); while α-ZOL positively E2 (%Δ: 5.61 -1.54, 9.85) female fetuses. urinary androstenedione 9.15 14.64, -3.30) both sexes, 37.13, 4.86, 79.34) amongst offspring. Findings support hypothesis that act endocrine disruptors humans, livestock. Additional work needed understand impacts on child health.

Language: Английский

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