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      Molecular Basis of Human Sperm Capacitation

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          Abstract

          In the early 1950s, Austin and Chang independently described the changes that are required for the sperm to fertilize oocytes in vivo. These changes were originally grouped under name of “capacitation” and were the first step in the development of in vitro fertilization (IVF) in humans. Following these initial and fundamental findings, a remarkable number of observations led to characterization of the molecular steps behind this process. The discovery of certain sperm-specific molecules and the possibility to record ion currents through patch-clamp approaches helped to integrate the initial biochemical observation with the activity of ion channels. This is of particular importance in the male gamete due to the fact that sperm are transcriptionally inactive. Therefore, sperm must control all these changes that occur during their transit through the male and female reproductive tracts by complex signaling cascades that include post-translational modifications. This review is focused on the principal molecular mechanisms that govern human sperm capacitation with particular emphasis on comparing all the reported pieces of evidence with the mouse model.

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          Most cited references325

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          Calcium signaling.

          Calcium ions (Ca(2+)) impact nearly every aspect of cellular life. This review examines the principles of Ca(2+) signaling, from changes in protein conformations driven by Ca(2+) to the mechanisms that control Ca(2+) levels in the cytoplasm and organelles. Also discussed is the highly localized nature of Ca(2+)-mediated signal transduction and its specific roles in excitability, exocytosis, motility, apoptosis, and transcription.
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            Fertilizing capacity of spermatozoa deposited into the fallopian tubes.

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              Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor.

              Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.

                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                27 July 2018
                2018
                : 6
                : 72
                Affiliations
                Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Tecnológicas , Buenos Aires, Argentina
                Author notes

                Edited by: Rafael A. Fissore, University of Massachusetts Amherst, United States

                Reviewed by: Christopher De Jonge, University of Minnesota Twin Cities, United States; Alexander Travis, Cornell University, United States

                *Correspondence: Mariano G. Buffone mgbuffone@ 123456ibyme.conicet.gov.ar

                This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2018.00072
                6078053
                30105226
                db64222e-5706-49a7-b27d-39cabb4f595f
                Copyright © 2018 Puga Molina, Luque, Balestrini, Marín-Briggiler, Romarowski and Buffone.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 February 2018
                : 19 June 2018
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 354, Pages: 23, Words: 23008
                Funding
                Funded by: Agencia Nacional de Promoción Científica y Tecnológica 10.13039/501100003074
                Award ID: PICT 2015-2294
                Categories
                Cell and Developmental Biology
                Review

                human sperm,capacitation,fertilization,hyperactivation,acrosomal exocytosis

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