Varicocele and diabetes mellitus (DM) have long been recognized to impair male fertility by interfering with both sperm parameters and production, however the molecular mechanism by which these effects occur remains largely unknown. Cyclooxygenases are important in spermatogenesis, but their ultrastructural localization in sperm cells and their role in male infertility have not yet established in humans. In the present study we presented the evidence of constitutive (COX-1) and inducible (COX-2) cyclooxygenase expression in healthy human sperm as well as their expression pattern associated with varicocele and DM. By Western blot analysis the comparison between normal and pathologic samples, showed a constitutive expression of both COX isoforms in the spermatozoa from healthy donors, a significant increase in COX-1 and COX-2 protein levels in both varicocele and diabetic semen samples. Our transmission electron microscopic (TEM) data with immunogold analysis provide the first morphological evidence of COX isoforms particular distribution in both healthy and pathological sperm, intriguingly revealing modifications in the amount of these enzymes. Taken together, our finding suggest that varicocele and DM may lead to male factor infertility by a mechanism involving an increased COXs expression in human spermatozoa evidencing that a detrimental effect at the molecular level exists, thus going beyond the abnormal sperm morphology described to date. In conclusion COX isoforms might play an important role in the pathogenesis and/or manteinance of infertility states and might represent a potential therapeutic targets in future strategies designed for the treatment of fertility disorders.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology