Sorbitol Can Fuel Mouse Sperm Motility and Protein Tyrosine Phosphorylation via Sorbitol Dehydrogenase1

Abstract

Energy sources that can be metabolized to yield ATP are essential for normal sperm functions such as motility. Two major monosaccharides, sorbitol and fructose, are present in semen. Furthermore, sorbitol dehydrogenase (SORD) can convert sorbitol to fructose, which can then be metabolized via the glycolytic pathway in sperm to make ATP. Here we characterize Sord mRNA and SORD expression during mouse spermatogenesis and examine the ability of sorbitol to support epididymal sperm motility and tyrosine phosphorylation. Sord mRNA levels increased during the course of spermatogenic differentiation. SORD protein, however, was first detected at the condensing spermatid stage. By indirect immunofluorescence, SORD was present along the length of the flagella of caudal epididymal sperm. Furthermore, immunoelectron microscopy showed that SORD was associated with mitochondria and the plasma membranes of sperm. Sperm incubated with sorbitol maintained motility, indicating that sorbitol was utilized as an energy source. Sorbitol, as well as glucose and fructose, were not essential to induce hyperactive motility. Protein tyrosine phosphorylation increased in a similar manner when sorbitol was substituted for glucose in the incubation medium used for sperm capacitation. These results indicate that sorbitol can serve as an alternative energy source for sperm motility and protein tyrosine phosphorylation.

Proteomic Analyses Reveal a Role of Cytoplasmic Droplets as an Energy Source during Epididymal Sperm Maturation

“…Typical protein modifications during epididymal sperm maturation include tyrosine phosphorylation and serine/threonine phosphorylation [48–51]. Interestingly, many phosphatase are also enriched in CDs, such as PPP1CC, PRSS21 and PRSS52, which are all involved in protein serine/threonine phosphorylation, and SORD, a protease associated with protein tyrosine phosphorylation [52–54], was also highly enriched in CDs. Thus, CDs also appear to provide modifying enzymes for sperm protein modifications.…”

Porcine sperm capacitation involves tyrosine phosphorylation and activation of aldose reductase

“…Recently, it has been reported that the activity of sperm SORD, the second enzyme of the polyol pathway, is also increased during capacitation (Baker et al 2010) and that sorbitol can also serve as an energy source for sperm motility and protein tyrosine phosphorylation via SORD (Cao et al 2009). However, under the present experimental conditions, the SORD inhibitor, CP-470,711, did not show any significant effects on the induction of hyperactivated motility.…”

Protein profile screening: reduced expression of Sord in the mouse epididymis induced by nicotine inhibits tyrosine phosphorylation level in capacitated spermatozoa

“…The biochemical modifications of spermatozoa during capacitation include modulation of enzyme activities, membrane modifications and protein tyrosine phosphorylation (De Jonge 2005). These tyrosine phosphorylation modifications are only partially known at the molecular level, but require an adequate supply of sufficient energy sources (Mukai & Okuno 2004, Ferramosca & Zara 2014, mainly including fructose (Cao et al 2009) and glucose (Urner & Sakkas 2003), the metabolic products (ATP and NADPH) of which appear to participate in signaling pathways by supporting the precise onset of protein tyrosine phosphorylation in the sperm flagellum leading to successful fertilization. The polyol pathway is related to epididymosomes that modulate sperm motility during the epididymal transit, which involves aldose reductase (ALDR) that uses NADPH to reduce glucose to sorbitol.…”