Mammalian sperm are not able to fertilize eggs immediately after ejaculation. They acquire fertilization capacity in the female tract in a process known as capacitation. Initially, capacitation was defined using fertilization as an end-point. However, a variety of evidence suggests that the functional changes occurring in the sperm during capacitation are not one event, but a combination of sequential and concomitant processes. These processes are associated with changes in the motility pattern (e.g. hyperactivation) and with preparation of sperm to undergo an agonist-stimulated acrosome reaction. At the molecular level, capacitation is associated with the activation of a cAMP signaling pathway, increase in intracellular pH, changes in the sperm plasma membrane potential, increase in tyrosine phosphorylation and with up-regulation of intracellular Ca2+ concentration ([Ca2+]i). In particular Ca2+ plays central roles in the regulation of both hyperactivation and the AR. However, the molecular mechanisms that control [Ca2+]i in sperm are not well established. The central hypothesis underlying this proposal posits that hyperactivation is the consequence of crosstalk between cAMP and Ca2+-depending signaling pathways. The objective of this proposal is to understand how Ca2+ and other signaling pathways (e.g. increase in pHi, cAMP and changes in Em) integrate during capacitation.

Public Health Relevance

Difficulties in earlier efforts to fertilize mammalian eggs in vitro were due mainly to a lack of comprehension of sperm physiology. This proposal is aimed to understand the molecular basis of sperm capacitation with emphasis in the regulation of the crosstalk between Ca2+ homeostasis and other signaling pathways in sperm. Accomplishment of these goals will provide tools for improving current Assisted Reproductive Technology (ART) methods and to identify novel contraceptive targets.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Moss, Stuart B
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University of Massachusetts Amherst
Veterinary Sciences
Schools of Earth Sciences/Natur
United States
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