STUDIES OF SPERM FUNCTION IN MAMMALIAN FERTILIZATION

哺乳动物受精过程中精子功能的研究

• 批准号: 3312950
• 负责人: PATRICIA J OLDS-CLARKE
• 金额: $ 8.02万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 1990-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3312950
• 关键词: acidity /alkalinity; acrosome; calcium; cell membrane; chromosomes; developmental genetics; enzyme inhibitors; fertility promoting drug; fluorescent dye /probe; galactosyltransferases; gene mutation; genes; laboratory mouse; lactalbumin; sperm; sperm capacitation; sperm motility

The t complex in the mouse affects the function of sperm in fertilization. Sperm carrying a t complex (t sperm) from t/+ mice fertilize most or all oocytes. We have recently shown that this apparent advantage of t sperm in fertilization is due to the dysfunction of sperm not carrying a t complex (+ sperm) from the same male. The mechanism by which + sperm become defective, and the specific abnormalities which prevent them from participating in fertilization, are not known. We have shown that sperm from t/+ mice (mutant sperm), after several hours in vitro, develop a unique type of non-progressive motility called "dancing." We now have preliminary evidence that mutant sperm also begin hyperactivation (HA) sooner than sperm from congenic +/+ mice (normal sperm). Thus mutant sperm may have several motility defects. Our preliminary evidence indicates that the timing of capacitation (CAP) is similar in mutant and normal sperm, implying that HA occurs earlier than CAP in mutant sperm. If so, the t complex provides a unique system in which to study the relationship between HA and CAP. The overall objective of this proposal is to characterize the abnormalities in motility of mutant sperm, using the novel quantitative motility parameters we have developed to measure various aspects of translational (whole-sperm) movement in individual mouse sperm; to determine the relationship of the motility abnormalities to CAP; and to explore several approaches to investigating the mechanism(s) causing the abnormal motility. Specifically, we will determine the kinetics of HA, CAP and dancing in mutant sperm, and determine the factors upon which each of these processes is dependent. We will also probe the subcellular site of the cause of the defective motility and determine whether dancing or the early onset of HA is dependent on the other known defect of mutant sperm, elevated surface galactosyl transferase activity. The proposed studies will increase our understanding of how the t complex affects sperm motility, and how the t complex affects HA and CAP, sperm functions essential for fertilization. These studies may also provide clues to the cause of the abnormal motility. Since it appears that HA is uncoupled from CAP in mutant sperm, these experiments may also contribute to our knowledge of the relationship between HA and CAP in normal sperm.

小鼠体内的t复合物影响精子的功能 施肥。 来自 t/+ 小鼠的携带 t 复合物的精子（t 精子） 使大部分或全部卵母细胞受精。 我们最近表明，这 T精子在受精方面的明显优势是由于 不携带 t 复合物（+精子）的精子功能障碍 同一个男性。 + 精子变得有缺陷的机制，以及 阻止他们参与的具体异常情况 在受精方面，尚不清楚。 我们已经证明来自 t/+ 的精子 小鼠（突变精子）在体外几个小时后，发育出一种独特的 一种称为“舞蹈”的非渐进运动。 我们现在有 初步证据表明突变精子也开始过度激活 (HA) 比同系 +/+ 小鼠的精子（正常精子）早。 因此 突变精子可能有多种运动缺陷。 我们的初步 有证据表明获能时间 (CAP) 相似 在突变精子和正常精子中，这意味着 HA 发生的时间早于 突变精子中的 CAP。 如果是这样，t复合体提供了一个独特的系统 研究HA与CAP之间的关系。 该提案的总体目标是描述 突变精子运动异常，使用新颖 我们开发用于测量的定量运动参数 平移（全精子）运动的各个方面 小鼠精子个体；来确定关系 CAP 运动异常；并探索几种方法 研究导致异常运动的机制。 具体来说，我们将确定 HA、CAP 和舞蹈的动力学 突变精子，并确定这些因素中的每一个 进程是依赖的。 我们还将探测亚细胞位点 运动缺陷的原因并确定是否 跳舞或 HA 的早期发作取决于其他已知的 突变精子缺陷，表面半乳糖基转移酶升高 活动。 拟议的研究将增加我们对如何 复合物影响精子活力，以及 t 复合物如何影响 HA 和 CAP，精子的功能对受精至关重要。 这些 研究还可能为异常原因提供线索 动力。 因为在突变体中 HA 似乎与 CAP 解偶联 精子，这些实验也可能有助于我们了解 正常精子中HA和CAP之间的关系。