Peroxisome Proliferator-Activated Receptors (PPARs) levels in spermatozoa of normozoospermic and asthenozoospermic men

Abstract

ABSTRACTInterest in the role of male factor in infertility continues to mount with defects related to sperm movement considered as one of the more severe forms of subfertility. The peroxisome proliferator-activated receptor gamma (PPARγ) primarily regulates the expression of target genes involved in energy control as well as lipid and glucose metabolism. Although the pivotal roles of these receptors on female fertility have been reported, there are limited studies addressing PPARs role(s) in the male. This study was designed to determine and compare PPARα, PPARβ and PPARγ mRNA expression in sperm cells of normozoospermic and asthenozoospermic men. In addition, flow cytometric analyses, immunofluorescence and western blot were used to evaluate PPARγ protein levels in spermatozoa. We have compared the sperm PPARs mRNA relative expression in 27 normozoospermic and 28 asthenozoospermic samples and monitored sperm PPARγ protein levels in 39 normozoospermic and 40 asthenozoospermic samples using flow cytometry. We have also assessed in a sub-group of seven normozoospermic and eight asthenozoospermic samples, PPARγ protein levels by western blotting. Relative expression of PPARγ mRNA in normozoospermic men was found to be significantly higher (P = 0.004) than in asthenozoospermic men while PPARα and PPARβ relative expression was similar in the two groups. Likewise, PPARγ showed a positive correlation with motility (r = 0.34; P < 0.05), sperm concentration (r = 0.33) and the percentage of progressive motile spermatozoa (r = 0.31). In agreement with the mRNA behavior, sperm PPARγ protein levels as measured by flow cytometry (P = 0.066) and western blot (P = 0.089) showed a tendency to be higher in normozoospermic than asthenozoospermic men. The present study proposes a link between PPARγ gene expression level and motility in human sperm.Abbreviations: PPARs: Peroxisome Proliferator-Activated Receptors; CASA: Computer Assisted Semen Analysis; TFA: Trans Fatty Acids; HTF: Human Tubal Fluid; PBS: Phosphate-Buffered Saline; PPP: Pentose Phosphate Pathway; PI3K: Phosphoinositide 3-Kinase; G6PDH: Glucose 6-Phosphate Dehydrogenase