Novel infertility mechanism suggested in men with metabolic syndrome

By Sally Robertson, B.Sc.Jan 21 2013

Men diagnosed with the metabolic syndrome appear to have reduced fertility potential despite the absence of leucocytospermia, report researchers.

Compromised sperm parameters in such individuals may instead be due to the direct effects of cytokines, they say.

"A proinflammatory state with oxidative stress associated with the syndrome may provide a novel explanation," write Ralf Henkel (university of the Western Cape, Bellville, South Africa) and colleagues in Andrologia.

The team's study of 50 men (24 with the metabolic syndrome and 26 controls) showed a significantly lower mean sperm concentration and total sperm count among those with the metabolic syndrome compared with controls, at 24.6 versus 43.2 (1 x 10⁶/mL) and 59.3 versus 122.0 (1 x 10⁶), respectively.

Total sperm motility was also significantly higher in those with than without the metabolic syndrome, while sperm vitality was significantly lower, as were concentrations of both free testosterone and free progesterone.

Furthermore, men with the syndrome had a significantly higher proportion of sperm with disturbed mitochondrial membrane potential and DNA fragmentation, at 62.4 versus 40.3% and 29.8 versus 17.8%, respectively.

"Since MetS [the metabolic syndrome] is considered a systemic inflammatory condition… the observation that patients with MetS have increased damage to mitochondrial function and sperm DNA appears conceivable, as both ROS [reactive oxygen species] and inflammatory cytokines have been repeatedly shown to cause damage to the sperm plasma membrane," note Henkel et al.

However, the researchers point out that their study design excluded patients with leucocytospermia and the ejaculates of participants from both groups of men were below the threshold for the diagnosis of leucocytospermia.

The team says that, although speculative, and assuming that increased serum levels of cytokines may cross into testicular tissue via the blood-testes barrier or into semen during ejaculation, inflammatory cytokines may potentially reduce sperm concentration, motility, and fertilizing capability.

This would provide a novel explanation for reduced fertility potential in men with obesity, the metabolic syndrome, or Type 2 diabetes, say Henkel et al, and also offers an interesting avenue for future research into the possible underlying mechanisms.

They add that the reductions in testosterone and progesterone concentrations may also be a result of the modulating effects of cytokines on the transcription and function of steroidogenic enzymes.

"These results warrant further investigation into confirming these conclusions and understanding possible mechanisms that may explain potential subfertility in male patients with MetS," concludes the team.

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