SPERM MEMBRANE LIPID CHANGES RELATED TO FERTILIZATION

与受精相关的精子膜脂质变化

• 批准号: 3447987
• 负责人: JOHN E PARKS
• 金额: $ 5.14万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447987
• 关键词: acrosome; cell membrane; electron microscopy; fertilization; membrane fusion; membrane lipids; phospholipids; sperm; sperm capacitation; thin layer chromatography

The concept that lipid changes in sperm cell membranes are a key to fertilization is well-founded, but the techniques now available to unravel these events have not been fully exploited. Spermatozoa, as produced in the male reproductive tract, must undergo important modifications prior to uniting with the egg. While numerous reports have appeared describing various pre-fertilization changes, called capacitation, and methods for inducing some type of capacitation have been developed. the molecular mechanisms responsible for this critical event remain unknown. The reports that capacitation includes modifications in sperm lipid composition is consistent with factors known to affect fusion in model membrane systems. Methods for characterizing these pre-fertilization changes in specific components of sperm membranes involved in the acrosome reaction and sperm-egg interaction resulting in conception will be exploited. Financial support is requested for a three year period to study the molecular mechanism of sperm capacitation, with emphasis on lipid composition of isolated membranes and the modifications to membrane lipids necessary for inducing the acrosome reaction. Specifically, the objectives of this research are to: (1) isolate purify and characterize the plasma membrane from the anterior sperm head and the outer acrosomal membrane; (2) conduct extensive lipid analyses of the isolated membranes, with special attention to lipid classes implicated in membrane fusion and consequently the acrosome reaction; and (3) modify the plasma membrane by enrichment or depletion of specific lipids using phospholipid exchange proteins discovered at Cornell and determine the effectiveness of these modifications on induction of the acrosome reaction and in vitro fertilization. This study should provide information which will be helpful in understanding the specific molecular events involved in membrane fusion and fertilization in general, and the acrosome reaction in particular. Detailed information about these biochemical events involved in fertilization will be useful in identifying and solving problems of infertility, improving methods for in vitro fertilization and in developing effective methods of contraception.

精子细胞膜中脂质的变化是 受精是有根据的，但现在可用的技术来解开 这些事件尚未得到充分利用。 精子，产生于 男性生殖道，必须经历重要的修改之前， 与鸡蛋结合。 尽管有许多报道称 各种受精前的变化，称为获能，以及用于 诱导某种获能的方法已经被开发出来了。分子 造成这一严重事件的机制仍然不明。 的报告 获能包括精子脂质成分的改变， 与已知影响模型膜系统中融合的因素一致。 用于表征这些受精前变化的方法， 参与顶体反应的精子膜成分， 将利用导致受孕的精卵相互作用。 申请为期三年的财政支助，以研究 精子获能的分子机制，重点是脂质 分离膜的组成和膜脂质的修饰 这是诱导顶体反应所必需的。 具体而言，目标 本研究的主要内容是：（1）血浆的分离纯化和性质研究 膜从精子头部前部和顶体外膜;（2） 对分离的膜进行广泛的脂质分析， 注意与膜融合有关的脂质类， 顶体反应;和（3）通过富集或 使用磷脂交换蛋白的特定脂质的消耗 在康奈尔大学发现的，并确定这些 对诱导顶体反应和体外 受精 这项研究提供的信息将有助于 了解膜融合中涉及的特定分子事件， 受精，特别是顶体反应。 关于这些生化事件的详细信息， 施肥将有助于确定和解决问题， 不孕症，改进体外受精方法和发展 有效的避孕方法。