High glucose concentrations per se do not adversely affect human sperm function in vitro

Abstract

Diabetes mellitus (DM) represents one of the greatest concerns to global health and it is associated with diverse clinical complications, including reproductive dysfunction. Given the multifactorial nature of DM, the mechanisms that underlie reproductive dysfunction remain unclear. Considering that hyperglycemia has been described as a major effector of the disease pathophysiology, we used an in vitro approach to address the isolated effect of high glucose conditions on human sperm function, thus avoiding other in vivo confounding players. We performed a complete and integrated analysis by measuring a variety of important indicators of spermatozoa functionality (such as motility, viability, capacitation status, acrosomal integrity, mitochondrial superoxide production and membrane potential) in human sperm samples after incubation with D-and L-glucose (5, 25, or 50 mM) for 24 and 48 h. No direct effects promoted by 25 or 50 mM D-glucose were found for any of the parameters assessed (PO0.05), except for the acrosome reaction, which was potentiated after 48 h of exposure to 50 mM D-glucose (P!0.05). Interestingly, non-metabolizable L-glucose drastically increased superoxide production (P!0.05) and suppressed sperm motility (P!0.05) and capacitation (P!0.05) after 24 h of treatment, whereas mitochondrial membrane potential (P!0.05), acrosomal integrity (P!0.01) and viability (P!0.05) were later decreased. The overall results suggest that high glucose levels per se do not influence human sperm function in vitro, which stresses the importance of other factors involved in DM pathology. Nevertheless, the absence of metabolizable glucose contributes to a severe impairment of sperm function and thus compromises male fertility. Free Portuguese abstract: A Portuguese translation of this abstract is freely available at

Lactate and Pyruvate Are Major Sources of Energy for Stallion Sperm with Dose Effects on Mitochondrial Function, Motility, and ROS Production

“…Similar high levels of ROS were observed with media containing very low levels of substrate, 0.25mM lactate and 0.25mM pyruvate, which likely produced ROS though the same mechanism after the pool of available substrate was exhausted. Others have also reported increased ROS production in human sperm incubated with non-metabolizable substrate (L-glucose) [12]. The proposed mechanism of ROS production described is also what occurs with addition of the ATP-synthase inhibitor, oligomycin, as discussed previously.…”

“…Inadequate metabolizable substrates can lead to mitochondrial dysfunction resulting in decreased motility and increased production of reactive oxygen species (ROS) leading to oxidative cell injury [12][13][14][15]. Most notably, oxidative stress can lead to lipid peroxidation, loss of sperm motility, loss of mitochondrial membrane potential and disruption of electron transport, oxidative DNA damage, as well as caspase activation, all leading to the intrinsic apoptotic pathway [16,17].…”

Investigating the Glycating Effects of Glucose, Glyoxal and Methylglyoxal on Human Sperm

“…This result was unsurprising as many studies investigating the chemical processes of glucose-mediated glycation have shown that this can take from 1 to 4 weeks, often as long as the turnover time of the proteins in vivo 37 – 39 . Furthermore, a recent study demonstrated that sperm parameters, such as motility and viability were unaffected by exposure to high levels of glucose in vitro 40 .…”

Oxidation of glyceraldehyde-3-phosphate dehydrogenase decreases sperm motility in diabetes mellitus

“…It is estimated that by 2035, the world will be near 5.92 billion people suffering from diabetes [3] .…”