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.
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.
| Gervasi, María G; Xu, Xinran; Carbajal-Gonzalez, Blanca et al. (2018) The actin cytoskeleton of the mouse sperm flagellum is organized in a helical structure. J Cell Sci 131: |
| Ritagliati, Carla; Luque, Guillermina M; Stival, Cintia et al. (2018) Lysine acetylation modulates mouse sperm capacitation. Sci Rep 8:13334 |
| Stival, Cintia; Ritagliati, Carla; Xu, Xinran et al. (2018) Disruption of protein kinase A localization induces acrosomal exocytosis in capacitated mouse sperm. J Biol Chem 293:9435-9447 |
| Romarowski, Ana; Velasco Félix, Ángel G; Torres Rodríguez, Paulina et al. (2018) Super-resolution imaging of live sperm reveals dynamic changes of the actin cytoskeleton during acrosomal exocytosis. J Cell Sci 131: |
| Luque, Guillermina M; Dalotto-Moreno, Tomas; Martín-Hidalgo, David et al. (2018) Only a subpopulation of mouse sperm displays a rapid increase in intracellular calcium during capacitation. J Cell Physiol 233:9685-9700 |
| Guidobaldi, Hector A; Hirohashi, Noritaka; Cubilla, Marisa et al. (2017) An intact acrosome is required for the chemotactic response to progesterone in mouse spermatozoa. Mol Reprod Dev 84:310-315 |
| Stival, Cintia; Puga Molina, Lis del C; Paudel, Bidur et al. (2016) Sperm Capacitation and Acrosome Reaction in Mammalian Sperm. Adv Anat Embryol Cell Biol 220:93-106 |
| Romarowski, Ana; Sánchez-Cárdenas, Claudia; Ramírez-Gómez, Héctor V et al. (2016) A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm. Biol Reprod 94:63 |
| Romarowski, Ana; Luque, Guillermina M; La Spina, Florenza A et al. (2016) Role of Actin Cytoskeleton During Mammalian Sperm Acrosomal Exocytosis. Adv Anat Embryol Cell Biol 220:129-44 |
| La Spina, Florenza A; Puga Molina, Lis C; Romarowski, Ana et al. (2016) Mouse sperm begin to undergo acrosomal exocytosis in the upper isthmus of the oviduct. Dev Biol 411:172-182 |
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