A NEW REGULATION MECHANISM OF MAMMALIAN SPERM CAPACITATION

CARLA RITAGLIATI; GUILLERMINA M LUQUE; CAROLINA BARO GRAF; DARIO KRAPF; CINTIA V STIVAL; MARIANO G BUFFONE

Chicago

Conferencia; 44th American Society of Andrology Annual Conference; 2019

American Society of Andrology

Mammalian sperm are unable to fertilize the egg immediately after ejaculation. To gain fertilization competence, they need to undergo a series of biochemical and physiological changes in the female reproductive tract, known as capacitation. Functionally, capacitation is associated with changes in sperm motility (hyperactivation) and with their ability to undergo the acrosome reaction. At the molecular level, it correlates with activation of the cAMP-PKA pathway, increase in intracellular pH and Ca2+ concentration, hyperpolarization of the plasma membrane potential, lipid modifications and increase in protein tyrosine phosphorylation. How these signaling pathways interact to induce hyperactivation and acrosomal responsiveness is not well understood. Since mature sperm are transcriptionally and translationally silent, they rely on postranslational modifications (PTM) more than any other cell type. Therefore, it is an exceptional model for the study of signaling pathways based on PTM. The importance of phosphorylation, an essential PTM in sperm physiology has been well established. On the other hand, acetylation of proteins, in spite of being as abundant and ubiquous as phosphorylation, has not been much explored in sperm. Recently, two groups identified 456 and 576 acetylated proteins in non-capacitated and capacitated human sperm respectively. Different acetylation profiles were observed in proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization, indicating that acetylation may be required for sperm capacitation and fertilization. In this context, the general aim of our work was to study the role of protein acetylation in the signaling cascade responsible for the acquisition of fertilizing capacity of mammalian sperm. Pharmacological hyperacetylation in non-capacitated sperm induced activation of PKA, hyperpolarization of the sperm plasma membrane, CatSper opening and Ca2+ influx, all capacitation-associated molecular events. In correlation with these results, sperm aquired both hyperactivated motility and acrosomal responsiveness, pointing towards the importance of lysine acetylation in sperm physiology