Metabolic Substrates Exhibit Differential Effects on Functional Parameters of Mouse Sperm Capacitation1

Abstract

Although substantial evidence exists that sperm ATP production via glycolysis is required for mammalian sperm function and male fertility, conflicting reports involving multiple species have appeared regarding the ability of individual glycolytic or mitochondrial substrates to support the physiological changes that occur during capacitation. Several mouse models with defects in the signaling pathways required for capacitation exhibit reductions in sperm ATP levels, suggesting regulatory interactions between sperm metabolism and signal transduction cascades. To better understand these interactions, we conducted quantitative studies of mouse sperm throughout a 2-h in vitro capacitation period and compared the effects of single substrates assayed under identical conditions. Multiple glycolytic and nonglycolytic substrates maintained sperm ATP levels and comparable percentages of motility, but only glucose and mannose supported hyperactivation. These monosaccharides and fructose supported the full pattern of tyrosine phosphorylation, whereas nonglycolytic substrates supported at least partial tyrosine phosphorylation. Inhibition of glycolysis impaired motility in the presence of glucose, fructose, or pyruvate but not in the presence of hydroxybutyrate. Addition of an uncoupler of oxidative phosphorylation reduced motility with pyruvate or hydroxybutyrate as substrates but unexpectedly stimulated hyperactivation with fructose. Investigating differences between glucose and fructose in more detail, we demonstrated that hyperactivation results from the active metabolism of glucose. Differences between glucose and fructose appeared to be downstream of changes in intracellular pH, which rose to comparable levels during incubation with either substrate. Sperm redox pathways were differentially affected, with higher levels of associated metabolites and reactive oxygen species generated during incubations with fructose than during incubations with glucose.

Human sperm anatomy and endocrinology in varicocele: role of androgen receptor

“…increased metabolism and overall energy expenditure, and previous studies have demonstrated that hormones induce capacitation together with energy expenditure (Aquila et al 2009, Goodson et al 2012. Therefore, we retain our previous finding that DHT interacting with AR may activate the receptor through phosphorylation (Aquila et al 2007), increasing metabolic activities and fueling capacitation in sperm.…”

The cell biology of mammalian fertilization

“…It not only serves as an energy source allowing spermatozoa to swim, but also functions to enable spermatozoa to fertilize eggs (Goodson et al, 2012;Okabe et al, 1986). Cholesterol, bicarbonate, intracellular Ca 2+ and many other factors are also involved in capacitation (Bailey, 2010;Evans, 2012;Florman and Ducibella, 2006;Yanagimachi, 1994); however, the precise molecular mechanisms underlying their action are yet to be clarified.…”

Differences in ATP Generation Via Glycolysis and Oxidative Phosphorylation and Relationships with Sperm Motility in Mouse Species

“…Furthermore, mouse sperm are not able to sustain ATP levels and progressive motility when treated with uncoupler agents (17,18) or respiratory inhibitors (10) in glucose-free media. However, two studies provided evidence that an active glycolytic pathway is essential for mouse sperm motility and male fertility.…”

“…The unique features of these isozymes may respond to the specificity of the localization of the glycolytic pathway in the principal piece of the sperm flagellum (35). A fully active glycolytic pathway is required for multiple steps in the fertilization cascade, including capacitation-dependent tyrosine phosphorylation, hyperactivated motility, and oocyte penetration (5,17,18,34,36,37). Taken together, evidence suggests that glycolysis is the main source of ATP required to sustain the motility of mouse spermatozoa.…”