REGULATION OF SPERM EXOCYTOSIS

精子胞吐作用的调节

• 批准号: 6520922
• 负责人: NICHOLAS L CROSS
• 金额: $ 10.46万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-19 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6520922
• 关键词: acid base balance; acrosome; antiport; artificial fertilization; cholesterol; clinical research; cow; exocytosis; fallopian tubes; fertilization; fluidity; fluorescence microscopy; fluorescence polarization; human subject; hydrogen transport; hydrogen transporting ATP synthase; lipid transport; male; membrane activity; membrane lipids; membrane transport proteins; sperm; sperm analysis; sperm capacitation; sphingomyelins

The acrosome of a sperm must undergo exocytosis before the sperm can fertilize an egg. Ejaculated mammalian sperm become capable of exocytosis during a poorly understood maturation process. The long-term objective of this project is to understand how acrosomal exocytosis is controlled. Sperm of some infertile men are unable to have normal acrosomal exocytosis, and a full understanding of how acrosomal exocytosis is controlled may suggest new ways to control fertility. Sperm lipids play an important role in the control of sperm exocytosis. Sperm must lose cholesterol to become acrosomally responsive. Loss of cholesterol increases the intracellular pH. Experiments will determine how human sperm pH is controlled so the mechanism of cholesterol's effect can be better understood. A structure-activity analysis will be performed to reveal what features of the cholesterol molecule are required for activity. The importance of cholesterol's ability to promote order among phospholipids will be studied by measuring fluorescence anisotropy of a membrane probe. A second lipid, sphingomyelin, has recently been shown to be involved in the control of acrosomal exocytosis, and experiments will test whether it acts by controlling cholesterol efflux or by serving as the source of signalling molecules. The cholesterol content of freshly ejaculated and oviductal bovine sperm will be compared to see if sperm lose cholesterol in the female tract.

在精子使卵子受精之前，精子的顶体必须经历胞吐作用。 射精的哺乳动物精子在我们知之甚少的成熟过程中能够进行胞吐作用。 该项目的长期目标是了解顶体胞吐作用是如何控制的。 一些不育男性的精子无法进行正常的顶体胞吐作用，充分了解顶体胞吐作用的控制方式可能会提出控制生育能力的新方法。精子脂质在控制精子胞吐作用中起着重要作用。 精子必须失去胆固醇才能产生顶体反应。 胆固醇的损失会增加细胞内的pH值。实验将确定如何控制人类精子的 pH 值，以便更好地了解胆固醇的作用机制。将进行结构-活性分析，以揭示活性所需的胆固醇分子的哪些特征。将通过测量膜探针的荧光各向异性来研究胆固醇促进磷脂有序的能力的重要性。 第二种脂质，鞘磷脂，最近被证明参与顶体胞吐作用的控制，实验将测试它是否通过控制胆固醇外流或作为信号分子的来源发挥作用​​。 将比较新鲜射精和输卵管牛精子的胆固醇含量，看看精子是否在女性管道中失去胆固醇。

项目成果

Structural features of sterols required to inhibit human sperm capacitation.

抑制人类精子获能所需的甾醇的结构特征。

• DOI: 10.1095/biolreprod.102.008607
• 发表时间: 2003
• 期刊: Biology of reproduction.
• 作者: Nimmo,MatthewR;Cross,NicholasL
• 通讯作者: Cross,NicholasL

Unesterified cholesterol content of human sperm regulates the response of the acrosome to the agonist, progesterone.

人类精子中的未酯化胆固醇含量调节顶体对激动剂黄体酮的反应。

• DOI: 10.1095/biolreprod55.1.19
• 发表时间: 1996
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Zarintash,RJ;Cross,NL
• 通讯作者: Cross,NL

Phosphatidylcholine enhances the acrosomal responsiveness of human sperm.

磷脂酰胆碱增强人类精子的顶体反应性。

• 发表时间: 1994
• 期刊: Journal of andrology
• 作者: Cross,NL