Wnt信号通路
连环素
下调和上调
细胞生物学
钙粘蛋白
生物
延伸率
胚胎
男科
内分泌学
内科学
化学
信号转导
细胞
基因
医学
生物化学
材料科学
极限抗拉强度
冶金
作者
Paola Rebuzzini,S Rustichelli,Lorenzo Fassina,Ilaria Canobbio,Maurizio Zuccotti,Silvia Garagna
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI