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: 6311629
• 负责人: GERALD SCHATTEN
• 金额: $ 25.34万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6311629
• 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.

在不孕症诊所中，卵胞浆内单精子注射（ICSI）治疗在全球范围内的迅速接受远远快于其分子和细胞生物学基础的基础知识。然而，目前还不可能绝对得出结论，使用ICSI的辅助生殖技术（ART）没有长期和意外的后果。由于为生物医学研究而故意创造人类受精卵不太可能摆脱宗教，伦理，道德，政治和财政的复杂性，本项目的目标是确定ICSI和自然受精之间的差异，并提供必要的科学数据，以了解这种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，因此本项目的总体目标是提供ICSI期间各种卵母细胞和精子操作在随后的胚胎发育和后代生产方面的后果的完整评估。不同生育能力的供体和恒河猴，以及非人灵长类动物和兔的卵母细胞。人类卵母细胞，因未受精或ICSI后失败而被丢弃，将使用非联邦资金进行研究。目标1。目的2.建立一个临床相关的系统，以探索ICSI的机制和安全性。研究卵细胞激活、第一细胞周期进程和ICSI后精子组分的命运;目的3。建立一种异种精子显微注射系统（人精子显微注射入兔卵母细胞），以检测人精子质量。我们建议使用从猴中获得的配子和胚胎以及从知情同意的患者中捐赠的临床丢弃的人类标本进行临床和临床前研究。总之，这些信息将推进：ICSI期间基因组联合的临床相关知识;可能转化为男性不育症诊断的应用;并可能很好地告知和保证不育患者及其医生，关于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。