Trophoblast Differentiation in In Vivo and In Vitro Fertilized Embryos

体内和体外受精胚胎的滋养层分化

• 批准号: 8248072
• 负责人: PAOLO RINAUDO
• 金额: $ 17.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248072
• 关键词: Adult; Affect; Apoptosis; Assisted Reproductive Technology; Behavior; Benign; Biological; Cattle; Cells; Chronic Disease; Congenital Abnormality; Couples; Data; Development; Disease; Elderly; Embryo; Embryonic Development; Environment; Exhibits; Fertilization in Vitro; Fetal Development; Fetal Growth; Gene Expression; Germ Cells; Gestational Diabetes; Goals; Human; In Vitro; Incidence; Infertility; Injection of therapeutic agent; Inner Cell Mass; Intervention; Intracytoplasmic Sperm Injections; Lead; Medical; Mitosis; Molecular; Mus; Pattern; Phenotype; Placentation; Pre-Eclampsia; Pregnancy Rate; Premature Labor; Procedures; Process; Stem cells; Structure; Syndrome; Testing; Tissues; Uterus; Very Low Birth Weight Infant; Woman; angiogenesis; animal data; body system; design; embryo/fetus; fetal; implantation; imprint; in vivo; malformation; offspring; research study; sperm cell; trophoblast

Infertility, a medical problem of widespread proportions, affects one in seven couples. Fortunately, treatment options are available, of which the most successful include assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI). These procedures require gametes to be fertilized in vitro and the resulting embryos to be cultured for 3 to 5 days before transfer to the uterus. Such interventions are very successful, providing excellent pregnancy rates. However, new evidence suggests that these procedures are not totally benign. Human studies show an increased incidence of maternal complications, such as preeclampsia, gestational diabetes and preterm labor in women who conceive by ART. Increased fetal complications, including low and very-low birth weights, imprinting disorders and congenital malformations, are also observed. Compelling animal data reveal that offspring produced by ART exhibit abnormal behavior, abnormal imprinting and embryonic gene expression as well as abnormal phenotypes, such as the large offspring syndrome in cattle. Undoubtedly, multiple mechanisms lead to these conditions and their causes are largely unknown. Most likely, they include altered gene expression and abnormal imprinting, which lead to changes in the structure and function of tissues, organs, and systems. The Fetal Onset of Adult Disease (FOAD) hypothesis holds that the embryo and fetus are more sensitive than the adult to environmental insults, which can result in structural malformations or functional changes that lead, in later life, to chronic diseases. Our preliminary data show that mouse embryos produced by IVF have a reduced number of trophoblast cells. Accordingly, we propose two specific aims to test the hypothesis that IVF compromises important aspects of embryonic and placental development. The goal of Aim 1 is to compare the gene expression patterns [inner cell mass (ICM) and trophoblast (TB)] and differentiative potential of embryos that are generated in vivo and in vitro. The goal of Aim 2 is to obtain functional correlates of the observed differences by assessing the effects of IVF on implantation. Thus, at the conclusion of these experiments, we shall have advanced our current understanding of the detrimental effects of in vitro development on the embryo, information that is crucial to designing culture conditions that better replicate the in vivo environment.

不孕不育是一个普遍存在的医学问题，影响着七分之一的夫妇。幸运的是， 有多种治疗选择，其中最成功的包括辅助生殖技术 (ART)，例如体外受精 (IVF) 和胞浆内单精子注射 (ICSI)。这些程序 要求配子在体外受精，并在之前培养所得胚胎3至5天 转移到子宫。此类干预措施非常成功，妊娠率很高。 然而，新的证据表明这些程序并不完全是良性的。人类研究表明 孕产妇并发症的发生率增加，例如先兆子痫、妊娠期糖尿病和早产 通过 ART 怀孕的妇女的分娩。胎儿并发症增加，包括低产和极低产 还观察到体重、印记障碍和先天畸形。令人信服的动物数据 揭示ART产生的后代表现出异常行为、异常印记和胚胎基因 表达以及异常表型，例如牛的大后代综合症。无疑， 多种机制导致这些情况，其原因很大程度上未知。最有可能的是，他们 包括基因表达的改变和印记的异常，这会导致结构和结构的变化 组织、器官和系统的功能。成人疾病胎儿发病 (FOAD) 假说认为 胚胎和胎儿比成人对环境损害更敏感，这可能导致结构性损伤 导致晚年慢性疾病的畸形或功能变化。我们的初步数据显示 体外受精产生的小鼠胚胎的滋养层细胞数量减少。据此，我们建议 两个具体目标是检验 IVF 损害胚胎和胎盘重要方面的假设 发展。目标 1 的目标是比较基因表达模式 [内细胞团 (ICM) 和 滋养层（TB）]和体内和体外产生的胚胎的分化潜力。目标是 目标 2 是通过评估 IVF 的影响来获得观察到的差异的功能相关性 植入。因此，在这些实验结束时，我们将推进我们当前的 了解体外发育对胚胎的有害影响，这些信息对于 设计更好地复制体内环境的培养条件。