Evidence map›Paper›PMID 41671867›Full record

ArticleEBioMedicine2026

Effects of gestational perfluorohexanesulfonic acid exposure at human realistic dose on social communication deficit in mouse offspring.

Shengmei Zhang, Chang Gao, Ruonan Li, Jia Lv, Jingjing Xu, Maohua Miao, Hong Liang, De-Xiang Xu, Bo Wang, Yichao Huang

Abstract read
In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Shengmei ZhangSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China.
Chang GaoSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China; Department of Pediatrics, Suzhou Hospital of Anhui Medical University, Anhui Medical University, Suzhou, 234099, China.
Ruonan LiSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China.
Jia LvSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China.
Jingjing XuSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China.
Maohua MiaoShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
Hong LiangShanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
De-Xiang XuSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China. Electronic address: xudex@ahmu.edu.cn.
Bo WangSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China. Electronic address: wangbdev@ahmu.edu.cn.
Yichao HuangSchool of Public Health and Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 230031, China; Department of Pediatrics, Suzhou Hospital of Anhui Medical University, Anhui Medical University, Suzhou, 234099, China. Electronic address: yichao.huang@ahmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly-life exposure to exogenous chemicals can disrupt neurodevelopment. Perfluorohexanesulfonic acid (PFHxS), a legacy PFAS widely used and detected globally, remains poorly studied for its neurotoxicity.

methodsCD-1 mice (n = 90 dams) were exposed to human-relevant dose of PFHxS from gestational day (GD) 0-17. PFHxS levels were measured in maternal plasma and foetal/offspring medial prefrontal cortex (mPFC) (GD 18, postnatal weeks [PNW] 4 and 10) using liquid chromatography tandem mass-spectrometry (LC-MS/MS). Offspring social behaviour was assessed with the Three-Chamber social test. Neurotransmitters in mPFC of PNW 10 offspring were profiled by LC-MS/MS, transcriptomics was performed on GD 18 and PNW 4 mPFC, GABAergic neurons were quantified by immunofluorescence, and glutamate decarboxylase (GAD) expression by western blotting. PFHxS-GAD interactions were examined via molecular docking and microscale thermophoresis (MST).

findingsMaternal plasma reached 5.1 ± 0.1 ng/mL, equivalent to human biomonitoring data, and PFHxS accumulated in foetal mPFC (68.1 ± 4.1 pg/g). PFHxS exposure induced social deficits at PNW 4 and 10, which were more pronounced in males. The mPFC of PFHxS exposed offspring exhibited an excitatory-tilted neurotransmitter profile, feature with reduced γ-aminobutyric acid (GABA, 90.6 ± 12.2 vs. 70.2 ± 4.3 μg/g, p = 0.008). The differentially expressed genes were enriched in GABAergic and synaptic signalling pathways. Despite unchanged percentage of GABAergic neuron and GAD expression, metabolite GABA/glutamate ratio was attenuated, suggesting impaired GAD function. Both molecular docking and MST suggested moderate-to-strong binding affinity between PFHxS and GAD, affecting GABA synthesis.

interpretationGestational PFHxS exposure at human-relevant levels impairs offspring social behaviour, likely via disruption of GAD-mediated imbalance in excitation/inhibition.

fundingThis work was provided by grants from the National Natural Science Foundation of China (82404221 and 82373586), Anhui Provincial Natural Science Foundation (2308085Y50 and 2408085QH275), Education Department of Anhui Province for Excellent Young Scientist (2022AH030076), and funding from Center for Big Data and Population Health of IHM (JKS2022020).

Indexed as

FluorocarbonsMaternal ExposurePrenatal Exposure Delayed EffectsSocial BehaviorSulfonic AcidsAnimalsFemaleGABAergic NeuronsGlutamate DecarboxylaseHumansMaleMiceMolecular Docking SimulationPrefrontal CortexPregnancyFluorocarbonsGlutamate Decarboxylaseperfluorohexanesulfonic acidSulfonic AcidsGABAergic signallingGestational chemical exposurePerfluorohexanesulfonic acidPFASSocial communication deficits

Identifiers

PMID41671867
PMCPMC12914860

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.