Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Canada.
Reprod Biomed Online. 2012 Jul;25(1):58-67. doi: 10.1016/j.rbmo.2012.02.012. Epub 2012 Mar 3.
The ERK/MAPK signalling cascade is involved in many cellular functions. In mice, the targeted ablation of genes coding for members of this pathway is often associated with embryonic death due to the abnormal development of the placenta. The placenta is essential for nutritional and gaseous exchanges between maternal and embryonic circulations, as well as for the elimination of metabolic waste. These exchanges occur without direct contact between the two circulations. In mice, the blood-placenta barrier consists of a triple layer of trophoblast cells adjacent to endothelial cells from the embryo. In the ERK/MAPK cascade, MEK1 and MEK2 are dual-specificity kinases responsible for the activation of the ERK1 and ERK2 kinases. Inactivation of Mek1 causes placental malformations resulting from defective proliferation and differentiation of the labyrinthine trophoblast cells and leading to a severe delay in the development and the vascularization of the placenta, which explains the embryonic death. Although Mek2(-/-) mutants survive without any apparent phenotype, a large proportion of Mek1(+/-)Mek2(+/-) double heterozygous mutants die during gestation from placenta anomalies affecting the establishment of the blood-placenta barrier. Together, these data reveal how crucial is the role of the ERK/MAPK pathway during the formation of the placenta.
ERK/MAPK 信号级联参与许多细胞功能。在小鼠中，靶向敲除该途径成员的编码基因通常与胎盘发育异常导致的胚胎死亡有关。胎盘对于母体和胚胎循环之间的营养和气体交换以及代谢废物的清除至关重要。这些交换发生在两个循环之间没有直接接触的情况下。在小鼠中，血胎盘屏障由与胚胎内皮细胞相邻的三层滋养细胞组成。在 ERK/MAPK 级联中，MEK1 和 MEK2 是双特异性激酶，负责激活 ERK1 和 ERK2 激酶。Mek1 的失活导致胎盘畸形，原因是腔隙滋养细胞的增殖和分化缺陷，导致胎盘发育和血管化严重延迟，这解释了胚胎死亡。尽管 Mek2(-/-)突变体在没有明显表型的情况下存活，但很大一部分 Mek1(+/-)Mek2(+/-)双杂合突变体在妊娠期间因影响血胎盘屏障建立的胎盘异常而死亡。这些数据共同揭示了 ERK/MAPK 途径在胎盘形成过程中的作用是多么关键。
