Trophoblast Differentiation in In Vivo and In Vitro Fertilized Embryos

不孕不育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)，如体外受精(IVF)和卵胞浆内单精子注射(ICSI)。这些程序 要求配子在体外受精，并将得到的胚胎培养3至5天 转移到子宫。这种干预措施非常成功，提供了极好的怀孕率。 然而，新的证据表明，这些手术并不完全是良性的。人体研究表明 产妇并发症发生率增加，如先兆子痫、妊娠期糖尿病和早产 通过艺术手段怀孕的妇女的分娩。胎儿并发症增加，包括低出生和极低出生 体重、印迹障碍和先天畸形也被观察到。令人信服的动物数据 揭示了ART产生的后代表现出异常的行为、异常的印记和胚胎基因 表达以及异常表型，如牛的大后代综合症。毫无疑问， 导致这些情况的机制有多种，其原因在很大程度上尚不清楚。最有可能的是，他们 包括基因表达改变和异常印迹，这会导致结构和 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侮辱更敏感，这可能导致结构性的 在晚年导致慢性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试管受精对胚胎和胎盘的重要方面的影响这一假设 发展。目标1的目标是比较基因表达模式[内细胞团(ICM)和 滋养层细胞(Tb)]和体内和体外产生的胚胎的分化潜力。的目标是 目标2是通过评估体外受精的效果来获得观察到的差异的功能相关性。 植入。因此，在这些实验的结论中，我们将推进我们目前的 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。

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.