Buska Katarzyna, Kedzierska Anna Ewa, Slawek Anna, Chelmonska-Soyta Anna
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Reprod Biol. 2017 Mar;17(1):89-96. doi: 10.1016/j.repbio.2017.01.003. Epub 2017 Feb 15.
Early preimplantation embryo-maternal communication is crucial for the establishment and development of pregnancy. Though the involvement of several candidate genes and proteins in this complex event has been described, the hierarchy of molecular networks governing this communication remains unknown. The primary objective of this study was to determine whether the presence of embryos in the uterine lumen stimulated or inhibited gene expression in the uterine tissue on day 3.5 post coitum. To answer this question, we investigated the gene expression of dedicated signal transduction pathways in the uterus of CD-1 mice during the preimplantation stage of pregnancy and compared this expression to mice with induced pseudopregnancy. The expression levels of 84 genes assigned to nine intracellular signalling pathways were investigated by real-time PCR. The results demonstrated down-regulation of the uterine gene expression in the majority of pathways. Among target genes, 27 were significantly (p<0.05) down-regulated, and only three were significantly up-regulated. A majority of the down-regulated genes were found to be regulated by the TGFB and NFKB pathways, which suggests that the presence of the embryo selectively regulates signalling within signal transduction pathways. One of the up-regulated genes crucial for early pregnancy was Ptgs2 (p<0.05). The increased amount of both Ptgs2 gene and protein products indicates that Ptgs2 expression may be the earliest positive embryo signal for implantation and pregnancy recognition in mice. In conclusion, our results not only underline which signalling pathways are regulated in embryo-maternal communication before implantation but also support "the quiet state hypothesis" of silencing gene expression.
早期植入前胚胎与母体的通讯对于妊娠的建立和发展至关重要。尽管已经描述了几种候选基因和蛋白质参与这一复杂事件，但控制这种通讯的分子网络层次仍然未知。本研究的主要目的是确定子宫腔内胚胎的存在是否会刺激或抑制交配后第3.5天子宫组织中的基因表达。为了回答这个问题，我们研究了妊娠植入前阶段CD-1小鼠子宫中特定信号转导通路的基因表达，并将其与诱导假孕小鼠的表达进行比较。通过实时PCR研究了分配到九个细胞内信号通路的84个基因的表达水平。结果表明，大多数通路中的子宫基因表达下调。在靶基因中，27个显著下调（p<0.05），只有3个显著上调。发现大多数下调基因受TGFB和NFKB通路调控，这表明胚胎的存在选择性地调节信号转导通路中的信号。对早期妊娠至关重要的上调基因之一是Ptgs2（p<0.05）。Ptgs2基因和蛋白质产物数量的增加表明，Ptgs2表达可能是小鼠植入和妊娠识别的最早阳性胚胎信号。总之，我们的结果不仅强调了植入前胚胎与母体通讯中哪些信号通路受到调控，还支持了基因表达沉默的“安静状态假说 ”。
