Elisabetta Baldi, Michaela Luconi, Lorella Bonaccorsi, Monica Muratori and Gianni Forti

Dipartimento di Fisiopatologia Clinica, Unita' di Andrologia, Universita' di Firenze, viale Pieraccini 6, I-50139 Firenze, Italy

TABLE OF CONTENTS

1. Abstract

2. Sperm capacitation: background

2.1. Modification in concentration of intracellular calcium and other ions during capacitation
2.2. Changes in membrane lipids and phospholipids during capacitation
2.3. Changes in protein phosphorylation and protein kinase activity during capacitation

2.3.1. Involvement of AC/cAMPPKA pathway in capacitation
2.3.2. Involvement of PKC in capacitation
2.3.3. Involvement of tyrosine phosphorylation in capacitation

3. Acrosome reaction (AR): background

3.1. Intracellular calcium during acrosome reaction
3.2. Phospholipases activation during acrosome reaction
3.3. Activation of protein kinases during acrosome reaction process

4. DNA fragmentation in human spermatozoa 4.1. Origin of sperm DNA damage

5. Perspective

6. Acknowledgements

7. References

1. ABSTRACT

Two processes, namely capacitation and acrosome reaction, are of fundamental importance in the fertilization of oocyte by spermatozoon. Physiologically occurring in the female genital tract, capacitation is a complex process, which renders the sperm cell capable for specific interaction with the oocyte. During capacitation, modification of membrane characteristics, enzyme activity and motility properties of spermatozoa render these cells able to penetrate oocyte investments and responsive to stimuli that induce acrosome reaction prior to fertilization. Physiological acrosome reaction occurs upon interaction of the spermatozoon with the zona pellucida protein ZP3. This is followed by liberation of several acrosomal enzymes and other constituents that facilitate penetration of the zona and expose molecules on the sperm equatorial segment that allows fusion of sperm membrane with the oolemma. The molecular mechanisms and the signal transduction pathways mediating the processes of capacitation and acrosome reaction have been partially defined, and appear to involve modifications of intracellular calcium and other ions, lipid transfer and phospholipid remodeling in sperm plasma membrane as well as changes in protein phosphorylation. Some of the kinases and phosphorylated proteins that are involved in the processes of capacitation and acrosome reaction have been now characterized. Characterization of sperm receptors to physiological inducers of acrosome reaction is in progress. This review summarizes the main signal transduction pathways involved in capacitation and acrosome reaction.Furthermore, the mechanisms underlying sperm DNA fragmentation are also briefly reviewed.