Expression of Eph-Ephrin A Molecules in Endometrium During Swine Embryo Implantation Examined Using Real-Time RT-PCR

Erythropoietin-producing hepatocellular receptor and its membrane-bound ligands （Eph-Ephrin） system could regulate some mammalian blastocyst attachment and spreading. In order to investigate the involvement of the Eph-Ephrin system in swine embryo attachment, mRNA expression of Eph-Ephrin molecules in endometrium was examined by real-time RT- PCR during embryo implantation in pigs. The results indicated that mRNA expressions of Eph A5, A7 and Ephrin A5 all continually increased from pregnancy day 13 to 24. Ephrin A3 mRNA expression significantly increased from day 13 to 18 and decreased from day 18 to 24, and the expression was the lowest on pregnancy day l 3 and the highest on day 18. However, Ephrin A4 mRNA expression was the lowest on pregnancy day 18 and the highest on day 24, and the expression decreased from day 13 to 18 and increased from day 18 to 24. Furthermore, mRNA expressions of Eph A5 and A7 were both found in other tissues, such as brain, muscle, intestine, stomach, etc. These findings suggest that the Eph-Ephrin system may play an important role in regulating the contact between blastocysts and endometrium during swine embryo implantation.

EPH-EPHRIN in human gastrointestinal cancers

Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.

猪胚胎附植部分因子研究进展

产仔数性状是养猪业中一个重要的经济性状,而胚胎附植对猪产仔数的高低有重要的影响。胚胎附植的调控涉及到多个生物学过程,在其中发挥作用的物质(附植因子)很多。作者针对孕酮、孕酮受体、雌二醇、雌激素受体α(ESR1)和促红细胞生成素产生肝细胞受体配体(Eph-ephrin)系统这几种附植因子的相关研究进行了归纳总结,重点阐述了这些因子在母胎对话过程中的时空表达、功能、突变、调控等方面的研究进展。其中,孕酮及其受体在猪胚胎附植活动中全程发挥着重要作用,黄体分泌的孕酮与母猪子宫内膜腔上皮、腺上皮、基质和肌细胞中的孕酮受体结合发挥作用,使这些组织细胞分泌多种附植因子,这些附植因子进一步参与胚胎附植过程。雌二醇是雌激素中含量最多、活性最强的一种激素,主要由卵巢颗粒细胞分泌,雌激素受体α是子宫内雌二醇的主要受体,二者结合可使母猪发情;此外,附植中处于游离状态的胚泡也分泌雌二醇,其是一个让母猪子宫内膜得以识别的信号,允许胚泡附植。Eph-ephrin系统作用广泛,其在人、小鼠和猪的胚胎附植过程中发挥着重要作用。系统中的EphA1、ephrin A1、EphA4等基因在猪的胚胎附植期表达量显著高于空怀猪,它们在子宫内膜附植点的表达量显著高于附植点间的部位,且ephrin A1的抑制表达会降低子宫内膜上皮细胞的迁移和黏附能力。这些附植因子都在猪胚胎附植活动中发挥着重要作用,对它们的深入研究将有利于明确猪胚胎附植调控机理,进一步揭示猪高繁机理。

铅暴露对斑马鱼胚胎心脏和脊柱发育的影响

[背景]铅分布广泛。铅暴露会干扰斑马鱼生命早期发育,但铅暴露影响斑马鱼骨骼发育和心脏发育的机制尚不清楚。[目的]探究醋酸铅暴露诱发的骨发育和心脏发育毒性的分子机制。[方法]将受精后3 h(3 hpf)斑马鱼胚胎暴露于不同浓度的醋酸铅(0、6、12、24和48μmol·L^(-1)),直至受精后5天(5 dpf)。统计5dpf的畸形表型,通过荧光定量PCR方法检测脊柱发育相关基因(bmp2b、bmp4、bmp9、runx2a、runx2b)和心脏发育相关基因(nkx2.5、myh6、myh7)的mRNA表达情况,分析发育相关调控通路Wnt/β-catenin通路(wnt5a、wnt8a、wnt10a、β-catenin)、TGF-β通路(tgf-β1、tgf-β2)相关基因和Eph-Ephrin信号中关键分子eph的mRNA表达情况。[结果]5dpf时与对照组相比,醋酸铅处理组斑马鱼出现包括脊柱弯曲和心包囊水肿的畸形表型。24、48μmol·L^(-1)醋酸铅组脊柱弯曲畸形率分别达到26.47%和71.52%,高于对照组(P<0.01)。qPCR结果发现,与对照组相比,48μmol·L^(-1)暴露组中,脊柱发育相关基因bmp2b、bmp4、bmp9、runx2a、runx2b的mRNA表达分别下调82.8%、58.0%、88.7%、85.5%、69.2%(P<0.05或P<0.01),心脏发育相关基因myh6、myh7、nkx2.5的mRNA表达分别下调63.7%、58.9%、55.2%(P<0.01),Wnt/β-catenin通路中wnt8a、β-catenin的mRNA表达分别下调了71.5%、47.3%(P<0.05或P<0.01),TGF-β通路中tgf-β1的mRNA表达下调了67.5%(P<0.01),eph的mRNA表达下调了86.9%(P<0.01)。[结论]醋酸铅通过下调脊柱发育和心脏发育相关基因的mRNA表达,以及抑制发育相关Wnt/β-catenin、TGF-β通路和Eph-Ephrin信号,引起脊柱弯曲和心包囊水肿等畸形表型,从而对斑马鱼心脏和骨骼产生发育毒性作用。