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Article

BPA Exposure Affects Mouse Gastruloids Axial Elongation by Perturbing the Wnt/β-Catenin Pathway

1
Laboratory of Biology and Biotechnology of Reproduction, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
2
Laboratory of Biochemistry, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Bassi 21, 27100 Pavia, Italy
3
University School for Advanced Studies Pavia (IUSS), 27100 Pavia, Italy
4
Department of Electrical, Computer and Biomedical Engineering (DIII), University of Pavia, Via Ferrata 5, 27100 Pavia, Italy
5
Centre for Health Technologies (CHT), University of Pavia, Via Ferrata 5, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(14), 7924; https://doi.org/10.3390/ijms25147924
Submission received: 11 June 2024 / Revised: 15 July 2024 / Accepted: 16 July 2024 / Published: 19 July 2024
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)

Abstract

Mammalian embryos are very vulnerable to environmental toxicants (ETs) exposure. Bisphenol A (BPA), one of the most diffused ETs, exerts endocrine-disrupting effects through estro-gen-mimicking and hormone-like properties, with detrimental health effects, including on reproduction. However, its impact during the peri-implantation stages is still unclear. This study, using gastruloids as a 3D stem cell-based in vitro model of embryonic development, showed that BPA exposure arrests their axial elongation when present during the Wnt/β-catenin pathway activation period by β-catenin protein reduction. Gastruloid reshaping might have been impeded by the downregulation of Snail, Slug and Twist, known to suppress E-cadherin expression and to activate the N-cadherin gene, and by the low expression of the N-cadherin protein. Also, the lack of gastruloids elongation might be related to altered exit of BPA-exposed cells from the pluripotency condition and their following differentiation. In conclusion, here we show that the inhibition of gastruloids’ axial elongation by BPA might be the result of the concomitant Wnt/β-catenin perturbation, reduced N-cadherin expression and Oct4, T/Bra and Cdx2 altered patter expression, which all together concur in the impaired development of mouse gastruloids.
Keywords: Bisphenol A; gastruloids; axial elongation; Wnt/β-catenin; cadherins; pluripotency Bisphenol A; gastruloids; axial elongation; Wnt/β-catenin; cadherins; pluripotency

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MDPI and ACS Style

Rebuzzini, P.; Rustichelli, S.; Fassina, L.; Canobbio, I.; Zuccotti, M.; Garagna, S. BPA Exposure Affects Mouse Gastruloids Axial Elongation by Perturbing the Wnt/β-Catenin Pathway. Int. J. Mol. Sci. 2024, 25, 7924. https://doi.org/10.3390/ijms25147924

AMA Style

Rebuzzini P, Rustichelli S, Fassina L, Canobbio I, Zuccotti M, Garagna S. BPA Exposure Affects Mouse Gastruloids Axial Elongation by Perturbing the Wnt/β-Catenin Pathway. International Journal of Molecular Sciences. 2024; 25(14):7924. https://doi.org/10.3390/ijms25147924

Chicago/Turabian Style

Rebuzzini, Paola, Serena Rustichelli, Lorenzo Fassina, Ilaria Canobbio, Maurizio Zuccotti, and Silvia Garagna. 2024. "BPA Exposure Affects Mouse Gastruloids Axial Elongation by Perturbing the Wnt/β-Catenin Pathway" International Journal of Molecular Sciences 25, no. 14: 7924. https://doi.org/10.3390/ijms25147924

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