Perfluorés et hormones thyroïdiennes impacts intergénérationnels à court et à long termes

IF 3.4 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Annales d'endocrinologie Pub Date : 2026-09-01 Epub Date: 2026-09-30 DOI:10.1016/j.ando.2026.102621

L. Butruille Mme

{"title":"Perfluorés et hormones thyroïdiennes impacts intergénérationnels à court et à long termes","authors":"L. Butruille Mme","doi":"10.1016/j.ando.2026.102621","DOIUrl":null,"url":null,"abstract":"<div><div>Thyroid hormones (TH) are critical regulators of neurogliogenesis, neural stem cell fate specification, oligodendrocyte differentiation and myelination during the perinatal period. Disruption of TH signaling during this sensitive developmental window may induce long-lasting alterations in adult neurogenesis and myelin development and repair, increasing vulnerability to demyelinating disorders. We investigated whether perinatal exposure to per- and polyfluoroalkyl substances (PFAS), known endocrine disruptors of TH homeostasis, produces persistent functional consequences on neurogliogenesis and myelin integrity. Using complementary in vivo and ex vivo models, we show that perfluorooctane sulfonate (PFOS), but not perfluorooctanoic acid (PFOA), alters both neurogenesis and oligodendrogenesis and impairs functional remyelination. In <em>Xenopus laevis</em> Tg(mbp:GFP-NTR), PFOS exposure inhibited spontaneous remyelination and altered visually guided behavior. In lysolecithin-demyelinated mouse cerebellar slices, PFOS reduced remyelination, an effect rescued by TH supplementation, supporting the involvement of altered TH signaling. In mice, maternal PFOS exposure during late gestation and lactation led to PFOS accumulation within offspring myelin and induced long-term alterations in subventricular zone (SVZ) neurogliogenesis. PFOS transiently shifted neural stem cell lineage specification toward oligodendrogenesis at the expense of neurogenesis during early postnatal stages, while impairing oligodendrocyte precursor cell maturation in adulthood. PFOS exposure was also associated with reduced numbers of adult-born dopaminergic interneurons in the olfactory bulb and altered olfactory memory in adult offspring. Ultrastructural analyses further revealed sustained thinning and disorganization of the myelin sheath. In vitro, PFAS altered the biophysical properties of myelin lipid membranes, indicating combined indirect endocrine and direct membrane effects.</div></div><div>Thyroid hormones (TH) are critical regulators of neurogliogenesis, neural stem cell fate specification, oligodendrocyte differentiation and myelination during the perinatal period. Disruption of TH signaling during this sensitive developmental window may induce long-lasting alterations in adult neurogenesis and myelin development and repair, increasing vulnerability to demyelinating disorders. We investigated whether perinatal exposure to per- and polyfluoroalkyl substances (PFAS), known endocrine disruptors of TH homeostasis, produces persistent functional consequences on neurogliogenesis and myelin integrity. Using complementary in vivo and ex vivo models, we show that perfluorooctane sulfonate (PFOS), but not perfluorooctanoic acid (PFOA), alters both neurogenesis and oligodendrogenesis and impairs functional remyelination. In <em>Xenopus laevis</em> Tg(mbp:GFP-NTR), PFOS exposure inhibited spontaneous remyelination and altered visually guided behavior. In lysolecithin-demyelinated mouse cerebellar slices, PFOS reduced remyelination, an effect rescued by TH supplementation, supporting the involvement of altered TH signaling. In mice, maternal PFOS exposure during late gestation and lactation led to PFOS accumulation within offspring myelin and induced long-term alterations in subventricular zone (SVZ) neurogliogenesis. PFOS transiently shifted neural stem cell lineage specification toward oligodendrogenesis at the expense of neurogenesis during early postnatal stages, while impairing oligodendrocyte precursor cell maturation in adulthood. PFOS exposure was also associated with reduced numbers of adult-born dopaminergic interneurons in the olfactory bulb and altered olfactory memory in adult offspring. Ultrastructural analyses further revealed sustained thinning and disorganization of the myelin sheath. In vitro, PFAS altered the biophysical properties of myelin lipid membranes, indicating combined indirect endocrine and direct membrane effects.</div>","PeriodicalId":7917,"journal":{"name":"Annales d'endocrinologie","volume":"87 5","pages":"Article 102621"},"PeriodicalIF":3.4000,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annales d'endocrinologie","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003426626001423","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/9/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Thyroid hormones (TH) are critical regulators of neurogliogenesis, neural stem cell fate specification, oligodendrocyte differentiation and myelination during the perinatal period. Disruption of TH signaling during this sensitive developmental window may induce long-lasting alterations in adult neurogenesis and myelin development and repair, increasing vulnerability to demyelinating disorders. We investigated whether perinatal exposure to per- and polyfluoroalkyl substances (PFAS), known endocrine disruptors of TH homeostasis, produces persistent functional consequences on neurogliogenesis and myelin integrity. Using complementary in vivo and ex vivo models, we show that perfluorooctane sulfonate (PFOS), but not perfluorooctanoic acid (PFOA), alters both neurogenesis and oligodendrogenesis and impairs functional remyelination. In Xenopus laevis Tg(mbp:GFP-NTR), PFOS exposure inhibited spontaneous remyelination and altered visually guided behavior. In lysolecithin-demyelinated mouse cerebellar slices, PFOS reduced remyelination, an effect rescued by TH supplementation, supporting the involvement of altered TH signaling. In mice, maternal PFOS exposure during late gestation and lactation led to PFOS accumulation within offspring myelin and induced long-term alterations in subventricular zone (SVZ) neurogliogenesis. PFOS transiently shifted neural stem cell lineage specification toward oligodendrogenesis at the expense of neurogenesis during early postnatal stages, while impairing oligodendrocyte precursor cell maturation in adulthood. PFOS exposure was also associated with reduced numbers of adult-born dopaminergic interneurons in the olfactory bulb and altered olfactory memory in adult offspring. Ultrastructural analyses further revealed sustained thinning and disorganization of the myelin sheath. In vitro, PFAS altered the biophysical properties of myelin lipid membranes, indicating combined indirect endocrine and direct membrane effects.

查看原文本刊更多论文

全氟和甲状腺激素的短期和长期代际影响

甲状腺激素（TH）是围产期神经胶质瘤发生、神经干细胞命运规范、少突胶质细胞分化和髓鞘形成的关键调节因子。在这个敏感的发育窗口期，破坏TH信号可能会导致成人神经发生和髓鞘发育和修复的长期改变，增加脱髓鞘疾病的易感性。我们研究了围产期暴露于全氟烷基和多氟烷基物质（PFAS）是否会对神经胶质瘤发生和髓磷脂完整性产生持续的功能影响，PFAS是已知的TH稳态内分泌干扰物。利用互补的体内和体外模型，我们发现全氟辛烷磺酸（PFOS），而不是全氟辛酸（PFOA），会改变神经发生和少突胶质发生，并损害功能性髓鞘再生。在非洲爪蟾Tg（mbp:GFP-NTR）中，全氟辛烷磺酸暴露抑制自发性髓鞘再生和改变视觉引导行为。在溶卵磷脂脱髓鞘小鼠小脑切片中，全氟辛烷磺酸减少了髓鞘再生，这是一种通过补充TH来挽救的效果，支持TH信号改变的参与。在小鼠实验中，母体妊娠晚期和哺乳期暴露于全氟辛烷磺酸导致后代髓鞘内全氟辛烷磺酸积累，并诱导心室下区神经胶质瘤发生的长期改变。在出生后早期，PFOS以牺牲神经发生为代价，短暂地将神经干细胞谱系规范转向少突胶质细胞，同时在成年期损害少突胶质细胞前体细胞的成熟。全氟辛烷磺酸暴露还与成年出生的嗅球中多巴胺能中间神经元数量减少和成年后代嗅觉记忆改变有关。超微结构分析进一步显示髓鞘持续变薄和解体。在体外，PFAS改变髓磷脂脂质膜的生物物理特性，表明间接内分泌和直接膜作用的结合。甲状腺激素（TH）是围产期神经胶质瘤发生、神经干细胞命运规范、少突胶质细胞分化和髓鞘形成的关键调节因子。在这个敏感的发育窗口期，破坏TH信号可能会导致成人神经发生和髓鞘发育和修复的长期改变，增加脱髓鞘疾病的易感性。我们研究了围产期暴露于全氟烷基和多氟烷基物质（PFAS）是否会对神经胶质瘤发生和髓磷脂完整性产生持续的功能影响，PFAS是已知的TH稳态内分泌干扰物。利用互补的体内和体外模型，我们发现全氟辛烷磺酸（PFOS），而不是全氟辛酸（PFOA），会改变神经发生和少突胶质发生，并损害功能性髓鞘再生。在非洲爪蟾Tg（mbp:GFP-NTR）中，全氟辛烷磺酸暴露抑制自发性髓鞘再生和改变视觉引导行为。在溶卵磷脂脱髓鞘小鼠小脑切片中，全氟辛烷磺酸减少了髓鞘再生，这是一种通过补充TH来挽救的效果，支持TH信号改变的参与。在小鼠实验中，母体妊娠晚期和哺乳期暴露于全氟辛烷磺酸导致后代髓鞘内全氟辛烷磺酸积累，并诱导心室下区神经胶质瘤发生的长期改变。在出生后早期，PFOS以牺牲神经发生为代价，短暂地将神经干细胞谱系规范转向少突胶质细胞，同时在成年期损害少突胶质细胞前体细胞的成熟。全氟辛烷磺酸暴露还与成年出生的嗅球中多巴胺能中间神经元数量减少和成年后代嗅觉记忆改变有关。超微结构分析进一步显示髓鞘持续变薄和解体。在体外，PFAS改变髓磷脂脂质膜的生物物理特性，表明间接内分泌和直接膜作用的结合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annales d'endocrinologie 医学-内分泌学与代谢

CiteScore

4.40

自引率

6.50%

发文量

311

审稿时长

50 days

期刊介绍： The Annales d''Endocrinologie, mouthpiece of the French Society of Endocrinology (SFE), publishes reviews, articles and case reports coming from clinical, therapeutic and fundamental research in endocrinology and metabolic diseases. Every year, it carries a position paper by a work-group of French-language endocrinologists, on an endocrine pathology chosen by the Society''s Scientific Committee. The journal is also the organ of the Society''s annual Congress, publishing a summary of the symposia, presentations and posters. "Les Must de l''Endocrinologie" is a special booklet brought out for the Congress, with summary articles that are always very well received. And finally, we publish the high-level instructional courses delivered during the Henri-Pierre Klotz International Endocrinology Days. The Annales is a window on the world, keeping alert clinicians up to date on what is going on in diagnosis and treatment in all the areas of our specialty.