Department of Animal Sciences, D.H. Barron Reproductive and Perinatal Biology Program, and Genetics Institute, University of Florida, Gainesville, FL 32611-0910, USA.
Sci Rep. 2013;3:1266. doi: 10.1038/srep01266. Epub 2013 Feb 12.
Objectives were to evaluate the role of canonical WNT signaling in development of the preimplantation embryo. Signaling was activated with 2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and inhibited with Dickkopf-related protein 1 (DKK1). Treatment of bovine embryos with AMBMP at day 5 after insemination decreased development to the blastocyst stage at day 7 and reduced numbers of trophectoderm and inner cell mass cells. At high concentrations, AMBMP caused disorganization of the inner cell mass. DKK1 blocked actions of AMBMP but did not affect development in the absence of AMBMP. Examination of gene expression in day 6 morulae by microarray revealed expression of 16 WNT genes and other genes involved in WNT signaling; differences in relative expression were confirmed by PCR for 7 genes. In conclusion, the preimplantation embryo possesses a functional WNT signaling system and activation of the canonical pathway can inhibit embryonic development.
目的是评估经典 WNT 信号通路在胚胎植入前发育中的作用。通过 2-氨基-4-(3,4-(亚甲二氧基)苄基氨基)-6-(3-甲氧基苯基)嘧啶(AMBMP)激活信号通路,并用 Dickkopf 相关蛋白 1(DKK1)抑制信号通路。在受精后第 5 天用 AMBMP 处理牛胚胎,会降低胚胎在第 7 天发育到囊胚阶段的能力,并减少滋养外胚层和内细胞团细胞的数量。在高浓度下,AMBMP 会导致内细胞团的紊乱。DKK1 阻断了 AMBMP 的作用,但在没有 AMBMP 的情况下,它不会影响胚胎的发育。通过微阵列对第 6 天桑椹胚的基因表达进行检查,发现了 16 个 WNT 基因和其他参与 WNT 信号通路的基因的表达;通过对 7 个基因的 PCR 验证,证实了相对表达的差异。总之,植入前胚胎具有功能性的 WNT 信号系统,激活经典途径可以抑制胚胎发育。