Caffeic acid phenethyl ester disrupts germ layer specification in Xenopus embryos

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-09-04 DOI:10.1016/j.reprotox.2025.109046

Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi

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Abstract

Xenopus embryo serves as an ideal model for teratogenesis assays to observe the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening of a chemical library with frog embryo, caffeic acid phenethyl ester (CAPE) was found to upregulate the FGF/MAPK pathway, disrupting germ layer formation in early development. Exposure to CAPE interfered with the formation of anterior-posterior body axis and of ectodermal derivatives such as eyes, dorsal fin and pigment cells. These inhibitory effects were achieved by promoting paraxial mesodermal specification and neural differentiation concomitant with a repression of epidermal and neural crest cell fates. This compound also induced the caudalization of anterior neural fate, thereby recapitulating the activity of the FGF/MAPK signals in the anterior-posterior patterning of neural tissue. Consistently, phosphorylation of extracellular signal-regulated kinase (ERK) was elevated in CAPE-treated cells, which was mediated by the FGFR1 and FGFR4 pathway. Together, these results suggest that CAPE functions as an activator of the FGF/MAPK signaling pathway, generating severe teratogenic effects on germ layer specification in vertebrate early development.

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咖啡酸苯乙酯对爪蟾胚胎胚层发育的影响

非洲爪蟾胚胎是一种理想的致畸实验模型，用于观察任何化合物对早期发育和成年组织稳态至关重要的细胞过程的影响。在我们对青蛙胚胎化学文库的筛选中，发现咖啡酸苯乙酯（CAPE）上调FGF/MAPK通路，在发育早期破坏胚层的形成。暴露于CAPE干扰了前后体轴和外胚层衍生物如眼睛、背鳍和色素细胞的形成。这些抑制作用是通过促进旁轴中胚层规范和神经分化，同时抑制表皮和神经嵴细胞命运来实现的。该化合物还诱导了前神经命运的尾状化，从而再现了神经组织前后模式中FGF/MAPK信号的活性。一致地，在cape处理的细胞中，细胞外信号调节激酶（ERK）的磷酸化水平升高，这是由FGFR1和FGFR4途径介导的。综上所述，这些结果表明CAPE作为FGF/MAPK信号通路的激活剂，在脊椎动物早期发育过程中对胚层形成产生严重的致畸作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.