Mammalian sperm must undergo a process termed capacitation to become competent to fertilize an egg. Capacitation renders the sperm competent by priming the cells to undergo a rapid exocytotic event called acrosomal exocytosis that is stimulated by the zona pelucida (ZP) of the egg or progesterone. Over the years, several biochemical events have been associated with the capacitation process;however, the question that has remained unanswered in investigations of capacitation is: What is the underlying reaction or set of reactions that transform the sperm cell from a state unresponsive to ZP or progesterone-stimulated acrosomal exocytosis to the state primed to respond to these stimuli? Our preliminary results demonstrate that the actin cytoskeleton plays a role in this process. Our long-term goal of this research: to elucidate the molecular mechanism whereby the actin cytoskeleton controls acrosomal exocytosis in mammalian sperm. In this proposal, we evaluate the establishment and stabilization of the primed state of acrosomal exocytosis that develops during the course of sperm capacitation. Additionally, we will examine the roles of intracelular calcium and actin in the destabilization of the primed state of acrosomal exocytosis that results in the propagation of the fusion of the outer acrosomal and plasma membranes. There are several human health-related reasons these studies are significant. For example, an understanding this process may lead to a better understanding of certain cases of male infertility and to the development of pharmacological approaches to interfere with this process, leading to new contraceptive agents. Most importantly, since actin has been implicated in exocytosis occurring in many types of somatic cells, information gathered from studying the less complicated sperm system will likely impact our understanding of secretion in other organ systems such as endocrine or digestive tissues.

Public Health Relevance

In this application, we will contribute to elucidate the molecular mechanism whereby the actin cytoskeleton controls acrosomal exocytosis in mammalian sperm. Investigating acrosomal exocytosis may lead to better approaches to certain cases of male infertility and to the development of new contraceptive agents. Information gathered from studying the sperm system will impact our understanding of secretion in other organ systems such as endocrine or digestive tissues.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Project (R01)
Project #
1R01TW008662-01A1
Application #
8210119
Study Section
International and Cooperative Projects - 1 Study Section (ICP1)
Program Officer
Liu, Xingzhu
Project Start
2012-03-09
Project End
2013-02-28
Budget Start
2012-03-09
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$53,520
Indirect Cost
$3,520
Name
Fund Institute Biol Y Med Experimental
Department
Type
DUNS #
971983572
City
Buenos Aires
State
Country
Argentina
Zip Code
1428
Caballero-Campo, Pedro; Buffone, Mariano G; Benencia, Fabian et al. (2014) A role for the chemokine receptor CCR6 in mammalian sperm motility and chemotaxis. J Cell Physiol 229:68-78
Buffone, Mariano G; Hirohashi, Noritaka; Gerton, George L (2014) Unresolved questions concerning mammalian sperm acrosomal exocytosis. Biol Reprod 90:112