Energy metabolism in mammalian sperm motility

Abstract

Mammalian sperm, the only cells that achieve their purpose outside their organism of origin, have to swim vigorously within the female reproductive tract to reach an oocyte. Flagellar dyneins drive sperm motility, which accounts for the consumption of high amounts of ATP. The two main ATP-producing metabolic pathways are compartmentalized in sperm: oxidative phosphorylation in the midpiece and glycolysis in the principal piece. The relative preponderance of these pathways has been discussed for decades (the so-called sperm energy debate). The debate has been muddled by species-specific variances and by technical constraints. But recent findings suggest that sperm from most mammalian species employ a versatile metabolic strategy to maintain motility according to the physiological environment. Different metabolic pathways likely coordinate by using exogenous and/or endogenous substrates in order to produce ATP efficiently. Defects in any of these pathways (glycolysis, mitochondrial oxidative phosphorylation, Krebs cycle, fatty acids oxidation, and ketone bodies oxidation, among others) may disturb sperm motility and be at the origin of male infertility. Understanding sperm bioenergetics is thus crucial for building new diagnostic tools, and for the development of treatments for patients presenting with low sperm motility. Some of these patients may benefit from personalized metabolic supplementations and dietary interventions.

Motility Assessment of Ram Spermatozoa

“…The Krebs cycle, also called the citric acid cycle or tricarboxylic acid cycle, occurs in the mitochondrial matrix ( Figure 3 B) catalysed by sperm-specific isoenzymes, reduces substrates used to fuel the electron transport chain in oxidative phosphorylation including NADH, flavin adenine dinucleotide (FADH 2 ) and guanosine triphosphate (GTP) or ATP ( Figure 3 C). Acetyl CoA used in the Krebs cycle can also be generated by other sources, such as fatty acid beta-oxidation and ketone body catabolism [ 49 , 54 , 55 , 56 ], however these mechanisms are not discussed in detail in this review.…”

“…As previously mentioned, the motility of a spermatozoon is dependent on the amount of energy generated by a combination of metabolic pathways, the Krebs cycle and oxidative phosphorylation in mitochondria and glycolysis which occurs in the fibrous sheath [ 40 , 49 ]. As such, sperm cell damage which affects the mitochondria, cell membrane and/or fibrous sheath in the principal piece of the flagellum, result in altered sperm motility by reducing the cell’s capacity for ATP production.…”

“…Pyruvate generated via glycolysis can be imported through specific transporters into the mitochondria and oxidised into acetyl coenzyme A (acetyl CoA). Acetyl CoA then enters the Krebs cycle which generates nicotinamide adenine dinucleotide (NADH) from NAD+, flavin adenine dinucleotide (FADH 2 ) from FAD+ and 1 molecule of either guanosine triphosphate (GTP) or ATP from guanosine diphosphate (GDP) or adenosine diphosphate (ADP), respectively [ 49 ]. The electrons conserved in NADH and FADH 2 are then used to reduce oxygen in the electron transport chain of oxidative phosphorylation.…”

“…ATP synthase (V) then transports these protons back to the mitochondrial matrix and utilises the proton-motive force to synthesise up to 34 molecules of ATP from ADP [ 50 ]. Figures created with BioRender.com (accessed on 25 November 2022) and largely adapted from figures created by Amaral [ 49 ] and Visconti [ 42 ].…”

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and the long-term storage of horse spermatozoa

“…In this review, it is extremely important to consider that most technologies in use for sperm preservation expose spermatozoa to, at least, sub-physiological and potentially highly toxic environments. The basic aspects of sperm metabolism have been recently reviewed (Gibb & Aitken 2016, Pena et al 2021, Amaral 2022), but in brief, energetic metabolism is the process in which ATP is generated from the oxidation of carbon-based molecules and the concurrent reduction of electron carriers to provide electrons for the mitochondrial generation of ATP via the electron transport chain. The energy released in these thermodynamically favourable processes is then harnessed to phosphorylate ADP to ATP (Quijano et al 2016.…”