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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030763-06
Application #
6387629
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Rankin, Tracy L
Project Start
1994-09-19
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
6
Fiscal Year
2001
Total Cost
$101,597
Indirect Cost
Name
Oklahoma State University Stillwater
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
City
Stillwater
State
OK
Country
United States
Zip Code
74078
Cross, Nicholas L (2004) Reorganization of lipid rafts during capacitation of human sperm. Biol Reprod 71:1367-73
Cross, Nicholas L (2003) Decrease in order of human sperm lipids during capacitation. Biol Reprod 69:529-34
Chattopadhyay, Sandip; Sun, Peng; Wang, Pengcheng et al. (2003) Fusion of lamellar body with plasma membrane is driven by the dual action of annexin II tetramer and arachidonic acid. J Biol Chem 278:39675-83
Nimmo, Matthew R; Cross, Nicholas L (2003) Structural features of sterols required to inhibit human sperm capacitation. Biol Reprod 68:1308-17
Cross, N L (2000) Sphingomyelin modulates capacitation of human sperm in vitro. Biol Reprod 63:1129-34
Cross, N L (1999) Effect of methyl-beta-cyclodextrin on the acrosomal responsiveness of human sperm. Mol Reprod Dev 53:92-8
Cross, N L (1998) Role of cholesterol in sperm capacitation. Biol Reprod 59:7-11
Cross, N L; Razy-Faulkner, P (1997) Control of human sperm intracellular pH by cholesterol and its relationship to the response of the acrosome to progesterone. Biol Reprod 56:1169-74
Cross, N L; Mahasreshti, P (1997) Prostasome fraction of human seminal plasma prevents sperm from becoming acrosomally responsive to the agonist progesterone. Arch Androl 39:39-44
Zarintash, R J; Cross, N L (1996) Unesterified cholesterol content of human sperm regulates the response of the acrosome to the agonist, progesterone. Biol Reprod 55:19-24

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