Impact of body mass index on seminal oxidative stress.

Male obesity has been linked with a reduction in sperm concentration and motility, an increase in sperm DNA damage and changes in reproductive hormones. Recent large observational studies have linked male obesity with a reduced chance of becoming a father. One of the potential underlying pathological mechanisms behind diminished reproductive performance in obese men is sperm oxidative stress. The primary aim of this study was to determine if sperm oxidative stress was more common in obese/overweight men. A total of 81 men had their body mass index (BMI) correlated with seminal reactive oxygen species (ROS) production (Nitro Blue Tetrazolium assay), sperm DNA damage (TUNEL), markers of semen inflammation (CD45, seminal plasma PMN elastase and neopterin concentration) and routine sperm parameters, together with reproductive hormones. The principal finding from this study was that oxidative stress did increase with an increase in BMI, primarily due to an increase in seminal macrophage activation. However, the magnitude of this increase was small and only of minor clinical significance as there was no associated decline in sperm DNA integrity or sperm motility with increasing ROS production. Increased BMI was also found to be significantly linked with a fall in sperm concentration and serum testosterone, and an increase in serum oestradiol.

Macrophage activity in semen is significantly correlated with sperm quality in infertile men.

The presence of leucocytes within semen has the potential to impair sperm function. Neutrophils and macrophages make up 95% of seminal leucocytes, with both having the ability to damage sperm via the generation of reactive oxygen species, proteases and the induction of apoptosis. Existing cytological techniques for quantifying leucocyte activity within semen (peroxidase, CD45) are less than ideal as they merely count the number of leucocytes, rather than assess their activity. Seminal plasma elastase effectively determines neutrophil activity, yet gives no insight into macrophage activity. Neopterin, a molecule released from activated macrophages, may be a useful marker for macrophage activity in the male reproductive tract. To examine this possibility a total of 63 asymptomatic subjects with male factor infertility and 11 fertile controls provided semen samples for measurement of various inflammatory markers. We were able to confirm for the first time that seminal plasma does indeed contain neopterin and that the levels of this macrophage activity marker are threefold higher in infertile than fertile men. Furthermore, seminal plasma neopterin concentration was significantly correlated with sperm oxidative stress, DNA fragmentation (TUNEL) and apoptosis (Annexin V), making it a useful marker of sperm quality. By contrast, seminal plasma elastase showed no correlation with any marker of sperm quality.

Gap junction uncoupling protects the heart against ischemia.

BACKGROUND: Many stimuli can successfully protect the heart against ischemia. We investigated whether gap junction uncoupling before ischemia was myoprotective. We also studied the function of the adenosine triphosphate-dependent potassium channel, which has been implicated in the mechanism of pharmacologic preconditioning, with respect to gap junction physiology. METHODS: Twenty-eight rabbit hearts were placed on a Langendorff perfusion apparatus. Five were given a 5-minute infusion of 1 mmol/L heptanol (a gap junction uncoupler), 5 were given 10 micromol/L 2,3-butanedione monoxime (an electromechanical uncoupler), and 6 were given no drug. The left anterior descending coronary artery was then occluded for 1 hour and reperfused for 2 hours. Six hearts received 10 micromol/L glybenclamide before heptanol to evaluate the role of the adenosine triphosphate-dependent potassium channel. Six hearts underwent ischemic preconditioning with 2 cycles of 5 minutes of global ischemia and reperfusion. Action-potential duration of the ischemic zone, left ventricular developed pressure, and coronary flow were measured continuously. Infarct size was determined at the end of reperfusion. RESULTS: Heptanol significantly reduced infarct size (from 46% +/- 2% to 22% +/- 5%, P <.01), an effect that was not prevented by glybenclamide. Butanedione monoxime decreased developed pressure but did not significantly reduce infarct size (46% +/- 5% vs 46% +/- 2%, P = not significant). There were no differences among groups with regard to developed pressure or action-potential duration. CONCLUSION: Directly blocking gap junctions preconditions the heart. This protection is not a direct result of a decrease in developed pressure before a prolonged ischemic period nor is it achieved through a mechanism involving the adenosine triphosphate-dependent potassium channel.