哺乳动物胚胎附植与中药保胎作用机制研究进展

附植是指哺乳动物囊胚滋养层细胞与母体子宫上皮细胞之间逐步建立组织生理上联系的过程。成功的附植有赖于胚泡与母体相互识别,胚泡发育与母体子宫变化的同步以及抑制母体的免疫排斥反应和母体接受性等一系列事件。这些事件又受到母体和胚泡的激素以及一些因子的调控。传统中药可通过提高孕酮的含量、类雌激素样作用、治疗子宫内膜炎的作用以及影响白血病抑制因子和白细胞介素1的表达量来促进山羊胚胎附植。文章主要论述了哺乳动物胚胎附植的机制以及中药对胚胎附植的影响,这有助于进一步阐明中药保胎的作用机理。     

MicroRNA调控胚胎植入研究进展

植入是胚胎与子宫内膜识别、接触并依附于子宫内膜上或进一步侵入、包埋于子宫内膜中的过程,是哺乳动物生殖生理的重要环节,这一过程对于胚胎能够在子宫持续的发育并最终获得成功的妊娠是必需的。成功的植入需要同步发育的正常胚胎、容受性的子宫内膜及母胎的和谐对话来实现。胚胎植入过程复杂而短暂,参与调控的因素有很多,包括microRNA。论文介绍了与植入相关microRNA的最新研究进展,包括microRNA对胚胎发育、子宫内膜的容受性等方面的作用,将为我们理解植入机制提供新的视角。     

胚胎植入研究概况

胚胎植入已成为生殖医学研究领域中尚未解决的热点问题。胚胎植入是一个非常复杂的过程,需要胚泡和子宫内膜之间的通讯和相互协同作用,被认为是调控雌性生育和发展避孕方法最理想的靶点和最关键的环节,与人类生殖健康关系极其密切。虽然最近在胚胎植入过程、影响因素、调控因子及细胞与分子机理等研究方面已取得了一些进展,但仍存在不少技术难题有待于进一步深入研究。文章简要综述了胚胎植入的概念、过程以及影响因素与调控因子,在此基础上介绍了胚胎植入的细胞与分子机理方面的研究概况,并对胚胎植入的研究和发展方向进行了探讨。     

胚胎植入及其分子机制研究进展

哺乳动物的胚胎植入是生殖过程的一个重要环节,是妊娠的关键。包括胚胎对母体子宫内膜的识别、黏附、侵入等过程。正常情况下,胚胎仅在一个极短的时间内有机会附着到子宫内膜上,即胚泡滋养层达到侵入状态,子宫内膜达到接受状态,且两者同步发生,胚泡才会成功植入。胚胎植入的成功必须具备许多条件,需要足够的激素分泌,合体滋养层细胞形成,以及胚泡与子宫内膜同步发育与相互配合等。这一过程的调控机制十分复杂,至今仍是生殖医学领域中尚未解决的问题。文章就胚胎植入的基本过程及其分子机制做简要综述。     

Equine placenta – A clinician's perspective. Part 1: Normal placenta – Physiology and evaluation

A complex organ, the equine placenta is responsible for fetal nourishment, protection from external and internal insults, and the production and/or metabolisation of various hormones. The endometrial cups are unique structures of the equine placenta that are responsible for producing an essential hormone for equine pregnancy, equine chorionic gonadotropin. Since mares have epitheliochorial placentae, with 6 layers of tissue separating maternal from fetal circulation, almost the entire surface of the chorioallantois must be attached to the maternal endometrium in order to support a developing fetus adequately. The only avillous areas of the normal chorioallantois are: the cervical star, sites of the endometrial cups, areas facing oviductal papillae, folds overlying major allantoic vessels, and fetal foot PADs (placental areas of degeneration). There are characteristic differences between the gravid and the nongravid horn of the chorioallantois. Allantoic vesicles, allantoic pouches, hippomanes, amniotic plaques and yolk sac remnants are normal features of the equine placenta. The clinician should thoroughly examine the entire placenta immediately after its expulsion. The most important aspect of this evaluation is to check for completeness of the chorioallantois, along with identifying any pathological lesions on the fetal membranes or the umbilical cord.     

Expression of amphiregulin during the pre- and post-implantation period in the mouse reproductive tract

In mammals, embryo implantation is an essential step in reproduction. Implantation is a phenomenon that involves crosstalk between the blastocyst and the maternal endometrium. However, the molecular basis of the connections between the blastocyst and endometrium is not yet fully understood. Amphiregulin is a member of the epidermal growth factor family and is known to be expressed in the luminal epithelium of the mouse uterus on 3.5 days post coitum (dpc). Thus, to clarify the mechanism of amphiregulin at fetomaternal interface, we analyzed the expression pattern of amphiregulin mRNA in the oviducts and uteri of pregnant and psuedopregnant mice by means of real-time PCR. Amphiregulin expression in the pregnant uterus dramatically increased on 2.5 dpc, peaked on 3.5 dpc, and declined by 5.5 dpc. Furthermore, to analyze the effect of the presence of an embryo on amphiregulin expression, we determined the expression pattern of amphiregulin mRNA in the uterus after embryo transfer on 0.5 and 1.5 dpc. A previous study showed that the expression of amphiregulin mRNA depends on the concentration of progesterone. However, our present results indicate that amphiregulin mRNA is upregulated by the presence of fertilized eggs in the lumen of the oviduct on 0.5 dpc.     

Infectious causes of pregnancy disorders]

During pregnancy infections can entail disorders in many different ways. Damage through direct transmission of pathogens to the fetus occurs in the first place. The organisms are transmitted transovarially, diaplacentally, via endometrium, before or after implantation, via amnion or by the semen when ascending through the infectious environment. Embryo transfer is a new way of transmission. The respective infective microorganisms either directly colonize in the embryo with the well known consequences (fetotrope pathogens) or they colonize the placenta thus indirectly leading to damages to the embryo (placentotrope pathogens). During the process various overlappings are possible. A second large group of disorders in pregnancy is caused by effects of infections of the mother without pathogens being transmitted to the embryo or the placenta. These diseases are postinfectious allergies, immune complex diseases, damages through microbial toxins or mediators and various other forms of infectious processes found with the mother. The third group of disorders in pregnancy is the result of complications caused by vaccinations of the mother during or shortly before pregnancy: postvaccinal allergies, diseases through vaccinal germs and different other postvaccinal damages or stress because of vaccination.     

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。     

环氧合酶-1和环氧合酶-2在兔早期妊娠子宫内膜及早期胚胎中的表达

环氧合酶(cyclooxygenase，Cox)是由花生四烯酸合成前列腺素的限速酶，而前列腺素在哺乳动物的生殖过程中起着很重要的作用。本试验采用RT—PCR方法对环氧合酶-1(Cox-1)及环氧舍酶-2(Cox-2)在早期妊娠兔子宫内膜中的表达进行了半定量研究和在早期胚胎中的表达定性研究。结果表明，Cox-1在早期妊娠兔子宫内膜中表达较平稳，呈组成型表达；在早期胚胎中各个时期均可以检测到Cox-1mRNA，表明它在早期胚胎发育过程中起作用。Cox-2在早期妊娠子宫内膜中的表达水平有很大差异，妊娠第l天表达水平较高，从第2天开始表达下降，到第6天表达又明显增加，第8天达到最高。Cox-2在囊胚之前的各个时期胚胎均未检测到，而在扩展胚泡和孵出胚泡中表达，Cox-2的时期特异性表达可能与兔胚泡孵出及胚胎着床等过程相关。     

Research Progress on the Function of Wnt Signaling Pathway in the Development of Bovine Placenta

Placenta is the link between the fetus and the maternal body during pregnancy.Therefore, the pregnancy outcome of the key was related by the normal development of the placenta.Wnt signaling pathway plays an important role in the development of embryo and placenta formation, several Wnt pathways which have been clear study and the formation process of early embryo and placenta in cattle are reviewed in this article,the early expression of the Wnt pathway components in the somatic cell nuclear transfer (SCNT) cattle and normal insemination of bovine embryos is introduced. The expression of DKK-1 and Fzd4 have a special role in the formation and development of early placenta, but its molecular mechanism is not clear. In addition, the Wnt signaling pathway is activated by inhibiting the MAP2K and GSK3, led to the inner cell mass and trophoblast cell number increased and blastocyst development speed. But it is similar to the extent of phosphorylation of E-cadherin and beta-catenin protein in the early placenta of cows with SCNT and normal insemination, therefore, the role of Wnt signaling pathway in the early formation and development of bovine placenta should be further understood and studied.     

Wnt信号通路在牛胎盘发育过程中的功能研究进展

胎盘是哺乳动物在妊娠期间胎儿和母体之间的联系枢纽,因此,胎盘发育是否正常在妊娠中起着关键的作用。Wnt信号通路在胚胎发育和胎盘形成的过程中有着重要的作用,作者通过回顾几条已经研究较为清楚的Wnt信号通路和牛早期胚胎和胎盘的形成过程,介绍了Wnt信号通路的组成部分在体细胞核移植（somatic cell nuclear transfer,SCNT）牛和正常人工授精的牛的胚胎早期表达,提出了DKK-1和Fzd4的表达对于早期胎盘形成和发育有特殊的作用。此外,抑制MAP2K和GSK3信号可以激活Wnt信号通路,增加内细胞团和滋养层细胞的数量,加速囊胚的发育。SCNT牛和正常人工授精的牛早期胎盘中E-cadherin和β-catenin蛋白的磷酸化程度相似,所以对于Wnt信号通路在牛胎盘的早期形成和发育中的作用还需进一步的了解和研究。     

Embryo gene expression in pig pregnancy

Pregnancy is a complex process in which significant changes occur continually in both the corpora lutea and in the endometrium of the females and varies depending on the embryonic, pre-implantation or foetal stages. In the embryonic stages, the majority of genes expressed in the pig embryo correspond to the loss of cellular pluripotency. In contrast, the implantation consists of three phases: elongation of the conceptus, adhesion and union of the embryo to the endometrial epithelium. During these phases, many factors are expressed, including growth factors, molecules that facilitate adhesion and cytokines. All these changes are ultimately regulated by different lipid and hormonal substances, specifically by progesterone, oestradiol and prostaglandins, which regulate the expression of many proteins necessary for the development of the embryo, endometrial remodelling and embryo–maternal communication. This paper is a review of primary gene regulatory mechanisms in pigs during different stages of implantation.     

白血病抑制因子及其受体与子宫内膜的关系

白血病抑制因子(LIF)是一种多生物活性的细胞因子,研究表明,LIF在人及动物的子宫内膜的腺上皮细胞、妊娠期蜕膜及胎盘上均有表达;胚泡是动物生殖过程中的关键,一些细胞因子起重要作用,它们能够充当子宫内膜微环境的"局部调节者",LIF对哺乳动物胚胎发育到胚泡阶段具有一定的作用,LIF在子宫内膜中特异性表达,促进胚胎生长发育和启动胚泡植入;LIF在生殖周期中影响子宫的功能及调节子宫内膜生长,这可能与LIF作用于子宫使其能发生蜕膜反应有关;LIF通过与LIF受体及gp130蛋白作用而发挥重要的生物学功能。LIF在哺乳动物早期妊娠中的作用机制具有重要意义。文章对LIF及其受体与子宫内膜的关系做了综述。     

Extracellular matrix in epitheliochorial,endotheliochorial and haemochorial placentation and its potential application for regenerative medicine

A placenta is defined as structural approximation of maternal and foetal tissues to perform physiological exchange. Associated processes of differentiation and the establishment of its cells take place within the extracellular matrix (ECM) that provides a rich environment of collagens, fibronectins, cytokines and other components. Placental ECM is promising for tissue regeneration purposes, because it has immune tolerance capacities that may cause only minimal rejections of transplants with immunological differences between donor and recipient. However, specific characteristics of ECM during evolution of the structurally very diverse mammalian placenta are not yet revealed. We here address the major aspects of placental types, that is non‐invasive (epitheliochorial), medium (endotheliochorial)‐to‐high (haemochorial) invasive nature of the interhemal barrier between the foetal and maternal blood system as well as their main components of ECM with special reference to species that are commonly used as animal models for human placentation and in the potential applications for regenerative medicine.