ASPECTS OF BLASTOCYST IMPLANTATION

囊胚植入的各个方面

基本信息

批准号：
8097047
负责人：
Sudhansu K Dey
金额：
$ 10.87万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
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/8097047
关键词：
Address Adhesions Animal Model Attenuated Basic Science Biology Birth Blastocyst Transfer Breast Cell Polarity Cell Proliferation Clinical Colon Carcinoma Complex Conceptions Contraceptive Agents Cytoskeleton Defect Development Down-Regulation E-Cadherin Embryo Transfer Endometrium Epithelial Epithelial Cells Epithelium Estrogens Event Family Female Female infertility Fertility Figs - dietary Functional disorder Gene Deletion Genes Goals Homeobox Homeobox Genes Human Human Biology Implant Investigation Knowledge Link Lung Luteal Phase Malignant neoplasm of ovary Mesenchymal Methylation Modeling Molecular Molecular Genetics Mus Ovarian Ovarian hormone Ovulation Pathway interactions Pattern Phase Phenotype Play Pregnancy Pregnancy Rate Pregnancy loss Progesterone Prostate Pseudopregnancy Publishing Readiness Refractory Regulation Reproduction Research Rest Role Science Scientist Screening procedure Signal Pathway Signal Transduction Simulate Site Specific qualifier value Spontaneous abortion Stimulus Stress Supplementation Testing Time Unwanted pregnancy Uterus Vagina Wild Type Mouse Woman base blastocyst cancer cell cancer therapy clinically relevant combat craniofacial cytokine editorial failure Implantation implantation improved innovation leukemia inhibitory factor male mouse model natural Blastocyst Implantation novel novel strategies overexpression pregnant preimplantation programs psychologic public health relevance research study small molecule tumor uterine receptivity

项目摘要

DESCRIPTION (provided by applicant): One prerequisite for mammalian reproduction is an effective reciprocal interaction between an implantation-competent blastocyst and the receptive uterus. The blastocyst will implant only when this molecular dialogue is established. The goal of this proposal is to better understand the mechanisms that direct uterine receptivity and nonreceptivity with the aim of improving female fertility. We will use conditionally gene-deleted mouse models to address the molecular basis of these events, since these models provide mechanistic information relevant to fertility in women. Human reproduction is complex and not very efficient. More than 30% of conceptions result in spontaneous abortion with most losses occurring around the time of implantation due to an inappropriate uterine milieu. Unwanted pregnancy loss causes psychological and economical stress to families, and is a challenging clinical problem. Based on our published and preliminary results, we hypothesize that homeobox-cytokine-Wnt signaling, involving Msx1, leukemia inhibitory factor (LIF) and Wnt5a, is critical for implantation. To address these questions, we will pursue the following specific aims in mice: (1) The first Specific Aim will test the hypothesis that Msx1 plays key roles in regulating various phases of uterine sensitivity to implantation by altering the luminal epithelial cell polarity and epithelial- mesenchymal interactions; (2) The second Specific Aim will test the hypothesis that Msx1 and LIF closely interact to direct various phases of uterine sensitivity; and (3) The third Specific Aim will test the hypothesis that overexpression of uterine Msx1 results in implantation failure, but extends the uterine preparedness to implantation. Our preliminary results with conditional deletion of uterine Msx1 and/or deletion of Lif hold great promise and have created a window of opportunity to generate molecular and genetic information on potential mechanisms by which the uterus becomes receptive or nonreceptive. This research is clinically relevant because Msx1 is downregulated in the human endometrium during the receptive phase (window of implantation).This simulates the situation in mice in which Msx1 is downregulated just prior to the initiation of implantation. The results derived from the proposed study using mouse models may help developing novel strategies to improve fertility in women.

描述（由申请人提供）：哺乳动物繁殖的先决条件之一是具有着床能力的囊胚和接受子宫之间有效的相互作用。只有当这种分子对话建立时，囊胚才会植入。该提案的目的是更好地了解指导子宫容受性和不容受性的机制，以提高女性生育能力。我们将使用条件性基因删除小鼠模型来解决这些事件的分子基础，因为这些模型提供了与女性生育力相关的机制信息。人类的繁殖很复杂，而且效率不高。超过 30% 的受孕会导致自然流产，其中大多数损失发生在植入期间，原因是子宫环境不当。意外流产给家庭带来心理和经济压力，是一个具有挑战性的临床问题。根据我们已发表的初步结果，我们假设涉及 Msx1、白血病抑制因子 (LIF) 和 Wnt5a 的同源盒-细胞因子-Wnt 信号传导对于植入至关重要。为了解决这些问题，我们将在小鼠中追求以下具体目标：（1）第一个具体目标将检验以下假设：Msx1 通过改变管腔上皮细胞极性和上皮细胞，在调节子宫对着床敏感性的各个阶段中发挥关键作用。间质相互作用； (2)第二个具体目标将检验Msx1和LIF密切相互作用以指导子宫敏感的各个阶段的假设； (3)第三个具体目标将检验子宫Msx1过度表达导致着床失败的假设，但将子宫准备延伸到着床。我们关于有条件删除子宫 Msx1 和/或删除 Lif 的初步结果具有很大的前景，并且创造了一个机会之窗，可以产生有关子宫变得接受或不接受的潜在机制的分子和遗传信息。这项研究具有临床相关性，因为 Msx1 在接受期（着床窗口期）在人类子宫内膜中下调。这模拟了小鼠中 Msx1 在着床开始前下调的情况。拟议的使用小鼠模型的研究得出的结果可能有助于开发新的策略来提高女性的生育能力。

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Galectin-1 markedly reduces the incidence of resorptions in mice missing immunophilin FKBP52.

Galectin-1 显着降低了缺失亲免蛋白 FKBP52 的小鼠的吸收发生率。

DOI：
发表时间：
2012-05
期刊：
影响因子：
4.8
作者：
Hirota, Yasushi;Burnum, Kristin E;Acar, Nuray;Rabinovich, Gabriel A;Daikoku, Takiko;Dey, Sudhansu K
通讯作者：
Dey, Sudhansu K

Extraembryonic heparin-binding epidermal growth factor-like growth factor deficiency compromises placentation in mice.

胚胎外肝素结合表皮生长因子样生长因子缺乏会影响小鼠的胎盘形成。

DOI：
发表时间：
2019
期刊：
影响因子：
3.6
作者：
Liu, Zitao;Skafar, Debra F;Kilburn, Brian;Das, Sanjoy K;Armant, D Randall
通讯作者：
Armant, D Randall

Phospholipase A2 activity in the rat uterus during early pregnancy.

妊娠早期大鼠子宫中磷脂酶 A2 的活性。

DOI：
发表时间：
1982-04
期刊：
影响因子：
0
作者：
Cox, C;Cheng, H C;Dey, S K
通讯作者：
Dey, S K

Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors.

植入前胚胎体外发育：胚胎之间的合作相互作用和生长因子的作用。

DOI：
10.1073/pnas.87.12.4756
发表时间：
1990-06-01
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
B. Paria;S. Dey
通讯作者：
S. Dey

Localization and binding of transforming growth factor-beta isoforms in mouse preimplantation embryos and in delayed and activated blastocysts.

转化生长因子-β亚型在小鼠植入前胚胎以及延迟和活化囊胚中的定位和结合。