PDF(Pubmed)
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.
摘要：
哺乳动物胚胎非常容易受到环境毒物（ET）的影响。双酚A(BPA),最扩散的ET之一，通过雌激素模拟和激素样特性发挥内分泌干扰作用，有害的健康影响，包括繁殖。然而,其在围植入期的影响尚不清楚.这项研究,使用gastruloids作为基于3D干细胞的胚胎发育体外模型，表明，在Wnt/β-catenin途径激活期间，BPA暴露会通过β-catenin蛋白减少而阻止其轴向伸长。Snail的下调可能阻碍了Gastroid的重塑，子弹和扭曲，已知抑制E-cadherin表达并激活N-cadherin基因，和N-cadherin蛋白的低表达。此外，缺乏腺样体伸长可能与暴露于BPA的细胞从多能性条件中退出的改变及其随后的分化有关。总之,在这里，我们表明，由BPA的gastruloids\'轴向伸长的抑制可能是伴随的Wnt/β-连环蛋白扰动的结果，N-cadherin表达降低，Oct4、T/Bra和Cdx2表达改变，所有这些都与小鼠类动物的发育受损一致。
