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: 7315922
• 负责人: PAOLO RINAUDO
• 金额: $ 11.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7315922
• 关键词: Adult; Affect; Apoptosis; Assisted Reproductive Technology; Behavior; Benign; Cattle; Cells; Chronic Disease; Condition; Congenital Abnormality; Congenital Disorders; Couples; Data; Development; Disease; Elderly; Embryo; Environment; Exhibits; Fertilization; Fertilization in Vitro; Fetal Diseases; Gene Expression; Germ Cells; Gestational Diabetes; Goals; Growth and Development function; In Vitro; Incidence; Infertility; Injection of therapeutic agent; Inner Cell Mass; Intervention; Intracytoplasmic Sperm Injections; Lead; Medical; Mitosis; Molecular; Mus; Numbers; Pattern; Phenotype; Placentation; Pre-Eclampsia; Pregnancy Rate; Premature Labor; Procedures; Process; Stem cells; Structure; Syndrome; Technology; Testing; Tissues; Uterus; Very Low Birth Weight Infant; Woman; angiogenesis; animal data; body system; day; design; embryo/fetus; fetal; human study; implantation; imprint; in vivo; malformation; reproductive; 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.

不孕症是一个普遍存在的医学问题，每七对夫妇中就有一对受到影响。幸运的是， 有各种治疗选择，其中最成功的包括辅助生殖技术 (ART)例如体外受精（IVF）和胞浆内精子注射（ICSI）。这些程序 要求配子在体外受精，产生的胚胎培养3至5天， 转移到子宫。这些干预措施非常成功，提供了极好的怀孕率。 然而，新的证据表明，这些程序并不完全良性。人类研究显示， 产妇并发症的发生率增加，如先兆子痫、妊娠糖尿病和早产 ART妊娠妇女的分娩。胎儿并发症增加，包括低出生和极低出生 还观察到体重、印记障碍和先天畸形。令人信服的动物数据 显示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，如牛的大后代综合征。毫无疑问， 导致这些病症的机制多种多样，其原因在很大程度上尚不清楚。很可能，他们 包括改变基因表达和异常印记，这导致结构的变化， 组织、器官和系统的功能。胎儿发病的成人疾病（FOAD）假说认为， 胚胎和胎儿比成人对环境损伤更敏感，这可能导致结构性损伤。 畸形或功能变化，导致在以后的生活中，慢性疾病。我们的初步数据显示 体外受精产生的小鼠胚胎滋养层细胞数量减少。因此，我们建议 两个具体的目的是检验IVF损害胚胎和胎盘重要方面的假设， 发展目的1的目的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能。的目标 目的2是通过评估IVF对以下方面的影响，获得所观察到的差异的功能相关性： 置入因此，在这些实验结束时，我们将推进我们的电流。 了解体外发育对胚胎的有害影响，这对 设计更好地复制体内环境的培养条件。