BIOMEDICAL BASIS OF INTRACYTOPLASMIC SPERM INJECTION (ICSI)

胞质内单精子注射 (ICSI) 的生物医学基础

• 批准号: 6440523
• 负责人: GERALD SCHATTEN
• 金额: $ 17.42万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6440523
• 关键词: Macaca mulatta; assistive reproductive technique; clinical research; cooperative study; egg /ovum; embryogenesis; human subject; human tissue; in vitro fertilization; laboratory rabbit; microinjections; microtubules; reproduction; sperm; technology /technique development

The rapid global acceptance of intracytoplasmic sperm injection (ICSI) therapy in infertility clinics as advanced far faster than the fundamental knowledge regarding its molecular and cell biological foundations. However, it is not yet possible to absolutely conclude that there are no long-lasting and unanticipated consequences of assisted reproductive technology (ART) using ICSI. Since the deliberate creation of human zygotes for biomedical research is unlikely to ever be free of religious, ethical,moral, political and financial complexities, the goal of this project is to identify the variations between ICSI and natural fertilization, and to provide the essential scientific data to understand the molecular and cell biological basis of this approach in a clinically relevant system. Since ICSI differs from natural fertilization in several ways, the overall objective of this project is to provide a complete evaluation of the consequences of various oocyte and sperm manipulations during ICSI in terms of subsequent embryo development and the production of offspring. To donors of varying fertility and from rhesus monkeys, as well as oocytes from the non-human primate and rabbit. Human oocytes, discarded as unfertilized or failures after ICSI, will be investigated using non-federal funding. Aim 1. To develop a clinically relevant system for exploring the mechanisms and safety of ICSI; Aim 2. TO investigate egg activation, first cell cycle progression and the fates of sperm components after ICSI; and Aim 3. To develop a heterologous system (human sperm microinjected into rabbit oocytes) to assay human sperm quality. We propose to perform clinical and preclinical studies using gametes and embryos obtained from monkeys, and donated, clinically discarded human specimens from informed consenting patients. Taken together, this information will advance: clinically-relevant knowledge about genomic union during ICSI; may translate into applications for the diagnosis of male infertility; and may well inform and reassure infertile patients and their physicians, about the safety and biomedical basis of this powerful, but still experimental, therapeutic approach.

全球范围内对不孕不育诊所中胞浆内单精子注射 (ICSI) 疗法的迅速接受，其进展速度远远快于对其分子和细胞生物学基础的基础知识的了解。然而，目前还不能绝对断定使用 ICSI 的辅助生殖技术 (ART) 不会产生长期和意外的后果。由于为生物医学研究而特意创造人类受精卵不可能摆脱宗教、伦理、道德、政治和财务的复杂性，因此该项目的目标是确定 ICSI 和自然受精之间的差异，并提供必要的科学数据，以了解该方法在临床相关系统中的分子和细胞生物学基础。由于 ICSI 在几个方面与自然受精不同，该项目的总体目标是对 ICSI 期间各种卵母细胞和精子操作对后续胚胎发育和后代产生的影响提供完整的评估。来自不同生育力的恒河猴的捐赠者，以及来自非人类灵长类动物和兔子的卵母细胞。因未受精或 ICSI 失败而被丢弃的人类卵母细胞将使用非联邦资助进行研究。目标1.开发临床相关系统来探索ICSI的机制和安全性；目标 2. 研究 ICSI 后卵子激活、第一次细胞周期进展以及精子成分的命运；目标 3. 开发异源系统（将人类精子显微注射到兔卵母细胞中）来测定人类精子质量。我们建议使用从猴子获得的配子和胚胎以及知情同意的患者捐赠的临床废弃的人类标本进行临床和临床前研究。总而言之，这些信息将推进： ICSI 期间基因组联合的临床相关知识；可能转化为诊断男性不育症的应用；并且可以很好地让不孕患者及其医生了解这种强大但仍处于实验阶段的治疗方法的安全性和生物医学基础，并让他们放心。