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：
7341165
负责人：
Bibhash Chandra Paria
金额：
$ 25.26万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7341165
关键词：
Animal Model Appendix Aromatase Aromatase Inhibitors C19 steroid Cells Comparative Study Cytochrome P450 DTR gene Defect Embryo Embryonic Development Enzymes Epidermal Growth Factor Epithelial Epithelium Estrogen Receptor 2 Estrogen Receptor alpha Estrogen Receptors Estrogens Event Failure Family suidae Female infertility Fertility Figs - dietary Gene Expression Genes Goals Grant Growth Factor Growth Factor Gene Hamsters Heparin Binding Hormonal Human Immunofluorescence Immunologic Immunohistochemistry In Situ Hybridization In Vitro Infertility Investigation Macaca mulatta Messenger RNA Modeling Molecular Morula Mus Oryctolagus cuniculus Ovarian Patient currently pregnant Play Pre-implantation Embryo Development Pregnancy Preparation Process Production Progesterone Proteins Rattus Regulation Reverse Transcriptase Polymerase Chain Reaction Role Source Staging Steroids Study models Sus scrofa Testing Time Uterus Western Blotting Woman Work base blastocyst cyclooxygenase 2 day embryo culture implantation in vitro Model in vivo insight leukemia inhibitory factor natural Blastocyst Implantation paracrine research study steroid hormone uterine receptivity ward

项目摘要

DESCRIPTION (provided by applicant): Ovarian progesterone is essential for implantation in all species studied. However, the requirement of embryonic estrogen in this process is still an unsettled issue, except in mice and rats in which embryos do not possess the machinery for estrogen synthesis. Implantation can occur in several species including hamsters and perhaps in humans in the absence of ovarian estrogen if progesterone is provided. However, our recent study shows that: (1) estrogen, but not progesterone, regulates the uterine expression of heparin binding EGF-like growth factor gene (Hegfl) in ovariectomized hamsters, and (2) Hegfl expression occurs in the uterine luminal epithelium surrounding the blastocyst at the time of implantation in the absence of circulating estrogen in progesterone-primed hypophysectomized pregnant hamsters. These results suggest that hamster blastocysts could be an alternative source of estrogen that acts locally to induce Hegfl gene expression in the uterus. Indeed, our preliminary experiments suggest the presence of cytochrome P450 aromatase protein in hamster morulae and blastocysts. Furthermore, the exposure of hamster morulae to a steroidal cytochrome P450 aromatase inhibitor in culture significantly inhibits the formation of blastocysts. These observations together with our preliminary results of estrogen receptor-alpha expression in preimplantation hamster embryos and uterus at the time of implantation led us to postulate that this species does not depend on ovarian estrogen, but requires embryonic estrogen to initiate embryonic and uterine changes required for implantation. However, neither the synthesis nor the role of embryonic estrogen in blastocyst formation, uterine receptivity and implantation in hamsters has been resolved. Thus, our specific aims to study in hamsters: (1) Do hamster preimplantation embryos produce estrogen? (2) Is embryonic estrogen required for morula-blastocyst transformation? (3) Is embryonic estrogen required for the establishment of uterine receptivity for implantation? (4) Does systemic estrogen induce uterine receptivity and implantation in the absence of embryonic estrogen? We will use multiple approaches including RT-PCR, in situ hybridization, immunohistochemistry, immunofluorescence, Western blotting, embryo culture and transfer and others to accomplish our goals. With better understanding of the mechanisms of embryo development and uterine receptivity for implantation, issues concerning fertility and infertility in women will be more effectively managed.

描述（由申请人提供）：卵巢孕酮对于所有研究的物种中植入至关重要。但是，在此过程中胚胎雌激素的需求仍然是一个未解决的问题，除了在小鼠和大鼠中，胚胎不具有雌激素合成的机械。如果提供孕激素，则可以在包括仓鼠，包括人类在内的几种物种中发生植入。但是，我们最近的研究表明：（1）雌激素（但不是孕激素）调节卵巢切除术中的肝素结合EGF类似EGF的生长因子基因（HEGFL）的子宫表达，（2）HEGFL表达发生在子宫内部围绕囊肿的囊括性上表达中的囊括性上表达，在囊括性上的囊括性上散发出循环的综合，并在囊括性上散发出循环的估算，这些杂物会在囊肿中的囊括性，并在囊括中散发出来。下生理仓鼠。这些结果表明，仓鼠胚泡可能是雌激素的替代来源，该雌激素在局部起作用，可诱导子宫中的HEGFL基因表达。实际上，我们的初步实验表明，仓鼠和胚泡中存在细胞色素P450芳香酶蛋白。此外，在培养中，仓鼠莫拉毛的暴露在培养物中的类固醇细胞色素P450芳香酶抑制剂会显着抑制胚泡的形成。这些观察结果以及我们在植入前植入前仓鼠胚胎和子宫中雌激素受体-Alpha表达的初步结果，导致我们假设该物种不取决于卵巢雌激素，但要求胚胎雌激素启动植入所需的胚胎和子宫变化。但是，既没有解决仓鼠中的胚胎雌激素在胚泡形成，子宫接受能力和植入仓鼠中的合成和作用。因此，我们的特定目的是在仓鼠中研究：（1）仓鼠植入前胚胎会产生雌激素吗？（2）Morula-Blastocyst转化需要胚胎雌激素吗？（3）建立子宫接受性以植入需要胚胎雌激素吗？（4）在没有胚胎雌激素的情况下，全身性雌激素会诱导子宫接受和植入吗？我们将使用多种方法，包括RT-PCR，原位杂交，免疫组织化学，免疫荧光，蛋白质印迹，胚胎培养和转移以及其他方法来实现我们的目标。有了更好地了解胚胎发育的机制和子宫接受的植入机制，将更有效地管理有关女性生育和不育的问题。