Hamster: A Unique Model for Studying Implantation

仓鼠：研究植入的独特模型

基本信息

批准号：
8063437
负责人：
Bibhash Chandra Paria
金额：
$ 11.81万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8063437
关键词：
Address Adenovirus Vector Age Amphiregulin Animal Model Appearance Area Assisted Reproductive Technology Atrial Natriuretic Factor Binding Biological Brain Brain natriuretic peptide C-Type Natriuretic Peptide Cardiac Cavia Cell Differentiation process Cell surface Cells Clinical Conceptions Contraceptive methods DTR gene Decidual Cell Decidual Cell Reactions Defect Detection Development Diagnostic Disease Embryo Emotional Endometrium Epithelium Estrogens Event Exhibits Family Family member Family suidae Female Figs - dietary Gel Gene Expression Genes Goals Grant Guanylate Cyclase Hamsters Heart Atrium Histamine Homeostasis Hormonal Horns Human Immunohistochemistry Implant In Situ Hybridization In Vitro Individual Infertility Inflammatory LIF gene Ligands Mediating Messenger RNA Modeling Molecular Monkeys Morula Mucin-1 Staining Method Mus Muscle Muscle relaxants Natriuretic Peptides Oryctolagus cuniculus Ovarian PTGS2 gene Papio Pattern Physiological Population Pregnancy Pregnancy loss Prevention Process Progesterone Progress Reports Property Prostaglandins Rattus Receptor Gene Receptor Signaling Regulation Relaxation Research Reverse Transcriptase Polymerase Chain Reaction Role Sepharose Signal Transduction Signaling Molecule Site Smooth Muscle Source Specific qualifier value Spontaneous abortion Staging Stem cells Stress Stromal Cells Study models Subfecundity System Testing Therapeutic Time To specify Up-Regulation Uterine Contraction Uterus Vasodilation Woman Work atrial natriuretic factor receptor A autocrine base blastocyst cell type cytokine design enterotoxin receptor failure Implantation human embryonic stem cell implantation improved in vivo insight mRNA Expression member mouse model myometrium novel paracrine peptide hormone polypeptide C preference pregnant prevent public health relevance receptor reproductive social tool trophoblast uterine contractility uterine receptivity

项目摘要

DESCRIPTION (provided by applicant): Each species has developed its own strategy for implantation. Using a cross- species heterologous microarray we identified C-type natriuretic peptide (CNP) as a possible implantation signaling molecule in hamsters which exhibit progesterone- dependent implantation similar to rabbits, pigs, monkeys and most likely in humans. CNP is the third member of the natriuretic peptide (NP) family which also includes atrial- and brain-NPs (ANP and BNP). All NPs act via two types of guanylyl cyclase (GC) receptors, GC-A and GC-B. CNP has more preference for GC-B, while ANP and BNP prefer GC-A. Our preliminary results show that while CNP signaling predominates at the implantation site of hamsters, both ANP/BNP and CNP signalings are active at the implantation sites of both mice and hamsters. These observations together with uterine relaxation properties of CNP and ANP, trophoblast outgrowth by BNP, induction of implantation by BNP, and infertility in GC-B null females suggest that NP signaling strongly influences the implantation process. Thus, we formulated a working hypothesis that NP ligand-receptor signaling influences several biologically and clinically important aspects of implantation: 1) muscular tone of the receptive uterus, 2) blastocyst-uterine cross talk prior to implantation, 3) trophoblast attachment, outgrowth and invasion, and 4) uterine stromal cell decidualization. Therefore, our Specific Aims are to study in hamsters: 1) influence of the blastocyst on the uterus prior to and at the time of implantation; 2) functions of NPs in regulation of uterine contractility prior to and during the time of implantation; and 3) the role of NP ligand-receptor signaling in initiation of implantation and decidualization. We will use multiple experimental approaches including qPCR, Northern and in situ hybridization, immunohistochemistry, in vivo adenoviral vector-driven gene inhibition, in vitro uterine contraction studies, and others to accomplish our goals. Deciphering the regulatory events required for implantation will provide insight into the potential causes of defects in implantation and infertility in women. Thus, these studies in hamsters that show progesterone-dependent implantation may provide useful information in the development of diagnostic and therapeutic tools that can be used in detection, prevention and treatment of female reproductive disorders, and improved technologies for assisted reproduction and contraception.

描述（由申请人提供）：每个物种都制定了自己的植入策略。使用跨物种异源微阵列，我们确定了C型纳替肽（CNP）为仓鼠中可能的植入信号分子，这些仓鼠表现出与兔子，猪，猴子相似的孕酮依赖性植入，并且很可能在人类中。 CNP是Natriaretic肽（NP）家族的第三个成员，其中还包括心房和脑NP（ANP和BNP）。所有NP通过两种类型的Guanylyl Cyclase（GC）受体GC-A和GC-B作用。 CNP对GC-B有更多的偏爱，而ANP和BNP更喜欢GC-A。我们的初步结果表明，尽管CNP信号传导在仓鼠的植入部位占主导地位，但ANP/BNP和CNP信号均在小鼠和仓鼠的植入部位都活跃。这些观察结果与CNP和ANP的子宫弛豫特性，BNP的滋养细胞生长，BNP诱导植入以及GC-B无效雌性中的不育症表明NP信号强烈影响植入过程。因此，我们提出了一个有效的假设，即NP配体 - 受体信号传导在植入的生物学和临床上影响几个重要方面：1）接受子宫的肌肉音调，2）胚泡 - 肠胃菜交叉交谈，3）3）the植入，3）Trophophast eactments intermant and Intrapement and Intrapsment and Integant，以及4）UTERININE sTROMAL STROM ALOM STROM ALOM STROMAL DIDIDICAID。因此，我们的具体目的是在仓鼠中研究：1）胚泡在植入前和植入时对子宫的影响； 2）NP在植入之前和期间的子宫收缩性调节的功能； 3）NP配体信号传导在植入和典型化开始中的作用。我们将使用多种实验方法，包括QPCR，北部和原位杂交，免疫组织化学，体内腺病毒载体驱动的基因抑制，体外子宫收缩研究以及其他实现我们的目标。解密植入所需的调节事件将洞悉妇女植入和不育的潜在原因。因此，在仓鼠中的这些研究表明孕激素依赖性植入可能会在开发诊断和治疗工具的开发中提供有用的信息，这些信息可用于检测，预防和治疗女性生殖疾病，以及改进的技术来辅助生殖和避孕。