Microphysiological Flow Batteries For Dynamic EDC Screening Of mESC-derived Thyroid Organoids

Anna M. Kip, Daniel J. Carvalho, Marta Nazzari, Mírian Romitti, James Waddington, Carlotta Branca, Conor Bryan, Barry Jutten, Whitney van de Vin, Prakash Patel, Rikke Poulsen, Martin Hansen, Simon Thomas, Stephen R. Pennington, Sabine Costagliola, Florian Caiment, Stefan Giselbrecht, Lorenzo Moroni
2026 · doi:10.64898/2026.05.07.722520
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The study aimed to improve endocrine disrupting chemical (EDC) toxicological testing by developing a thyroid-on-chip platform that combines mouse embryonic stem cell–derived thyroid organoids with organ-on-chip technology and downstream multi-omics. Using a reversibly-sealed microphysiological flow battery to scale dynamic organoid culture and enable controlled chemical exposure, the authors exposed the organoids to four EDC classes and found transcriptomic and proteomic molecular signatures of thyroid disruption, including effects at very low concentrations (1 nM). The key limitation explicitly acknowledged is that conventional assays based on 2D cultures and animals do not recapitulate human thyroid physiology and offer limited mechanistic insight, which this paper addresses rather than demonstrating equivalence to human end-organ physiology. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Endocrine disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of dysregulating the production of thyroid hormones. Traditional thyroid toxicological assays rely on 2D cell cultures and animal models, both of which fail to accurately recapitulate human thyroid physiology and provide limited mechanistic insight into EDC toxicity. To overcome these limitations, we report a novel thyroid-on-chip platform integrating mouse embryonic stem cell–derived thyroid organoids with advanced organ-on-chip (OoC) technology and downstream multi-omics analysis. The platform leverages a reversibly-sealed microphysiological flow battery (MFB) to allow scale up of dynamic organoid culture and controlled chemical exposure while reducing operational complexity. Upon EDC exposure, transcriptomic and proteomic analysis revealed new molecular signatures of thyroid disruption across four different EDC classes, even at very low EDC concentrations (1nM), validating the capacity of this system to mechanistically dissect EDC-induced responses. This represents an integrated platform consists of an advanced physiologically relevant assay framework for next-generation endocrine toxicity testing, bridging the gap between in vitro screening and in vivo thyroid physiology.
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Abstract Endocrine disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of dysregulating the production of thyroid hormones. Traditional thyroid toxicological assays rely on 2D cell cultures and animal models, both of which fail to accurately recapitulate human thyroid physiology and provide limited mechanistic insight into EDC toxicity. To overcome these limitations, we report a novel thyroid-on-chip platform integrating mouse embryonic stem cell–derived thyroid organoids with advanced organ-on-chip (OoC) technology and downstream multi-omics analysis. The platform leverages a reversibly-sealed microphysiological flow battery (MFB) to allow scale up of dynamic organoid culture and controlled chemical exposure while reducing operational complexity. Upon EDC exposure, transcriptomic and proteomic analysis revealed new molecular signatures of thyroid disruption across four different EDC classes, even at very low EDC concentrations (1nM), validating the capacity of this system to mechanistically dissect EDC-induced responses. This represents an integrated platform consists of an advanced physiologically relevant assay framework for next-generation endocrine toxicity testing, bridging the gap between in vitro screening and in vivo thyroid physiology. Competing Interest Statement S.R.P. is co-founder and chief scientific officer of Atturos ltd.

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[{'doi': None, 'name': 'Horizon 2020', 'awards': ['825745']}]

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License: CC-BY-NC-ND-4.0