Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation

Abstract

After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract. During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them. The molecular basis of the regulation of this process is still not fully understood. Sperm are both transcriptionally and translationally silent, therefore post-translational modifications are essential to regulate their function. The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes. Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation. Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm. Its presence is significantly reduced in mature cauda sperm. Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent. Our results indicate that the modulation of O-GlcNAcylation takes place during sperm maturation and suggest a role for this post-translational modification in this process.

The impact of epididymal proteins on sperm function

“…Several posttranslational modifications (PTMs), such as phosphorylation, glycosylation (Baker 2016) and O-GlcNAcylation (Tourzani et al 2018) of sperm proteins occur during epididymal sperm maturation. The importance of the PTMs is still unclear, but as sperm are transcriptionally silent cells, PTMs provide a means of controlling the protein activity in sperm.…”

Molecular and Cellular Aspects of Mammalian Sperm Acrosomal Exocytosis

“…de la activación de la vía AMPc/PKA. Por el contrario, el cambio en el patrón de motilidad a un estado hiperactivado, es completamente dependiente de la producción temprana de AMPc por sAC y consecuente activación de PKA (Tourzani et al, 2018).…”

Caput Ligation Renders Immature Mouse Sperm Motile and Capable to Undergo cAMP-Dependent Phosphorylation

“…Capacitation is associated with the activation of several signaling pathways including but not limited to an increase in cAMP levels with the consequent activation of a protein phosphorylation cascade. Importantly, in immature sperm, phosphorylation is impaired even in the presence of exogenous permeable cAMP analogues [ 11 , 12 ].…”

“…In particular, epididymal maturation is associated with inactivation of the serine/threonine protein phosphatase 1 gamma Ppp1cc (also known as PP1γ2) [ 20 , 21 ]. More recently, our group has shown that protein O-GlcNAcylation changes in sperm during epididymal maturation [ 12 ]. Immature caput sperm exhibited high O-Linked β-N-Acetylglucosamine (O-GlcNAc) Transferase (OGT) protein levels corresponding with high levels of protein O-GlcNAcylation while mature cauda sperm exhibited levels of OGT and O-GlcNAcylation significantly lower [ 12 ].…”

“…More recently, our group has shown that protein O-GlcNAcylation changes in sperm during epididymal maturation [ 12 ]. Immature caput sperm exhibited high O-Linked β-N-Acetylglucosamine (O-GlcNAc) Transferase (OGT) protein levels corresponding with high levels of protein O-GlcNAcylation while mature cauda sperm exhibited levels of OGT and O-GlcNAcylation significantly lower [ 12 ]. The relation between O-GlcNAcylation and phosphorylation pathways has been documented in somatic cells [ 22 , 23 , 24 ].…”