Analysis of Sperm Motility Related to Transcriptional Alterations of Mitocondrial Genes in Males Affected by Infertility

Abstract

Infertility is a problem afflicting about 1/6 couples, and in 40% of cases this is primarily due to the male. Male infertility is a multifactorial pathology and it seems mainly related to sperm motility or sperm number. However, a diagnosis of infertility is frequently not followed by a precise explanation of its cause, reflecting our poor understanding of the spermatogenesis-related regulatory mechanisms and gene expression profiles. Therefore, this study was design to investigate the relative gene expression of a specific gene profile in ejaculate spermatozoa of men affected by infertility. This profile included 13 mitochondrial gene encoding subunits of respiratory chain and 7 nuclear sperm motility-related genes. We used values of progressive sperm motility (PR) to separate subjects affected by infertility into two groups, showing PR values higher (H group) or lower (L group) than the mean of the sample, and to classify fertile men (control group). We did not obtain a statistically significant difference in nuclear gene expression patterns in spermatozoa among these three groups. On the other hand, we observed an over-expression in 11/13 tested mitochondrial genes in the population of infertile males with altered sperm motility compared to the control group. This over-expression led us to speculate that there is an abnormal mRNA transcription of these 11 subunits, that impaired the normal energy supply ensuring sperm motility. Regarding the under-expression of 2/13 tested mitochondrial genes, we could assume that the spermatozoa mtDNA has accumulated mutations involving these two genes (CYB and ND4L). In conclusion, our results will provide useful information for the development of molecular diagnostic tools for clinical assessment of sperm health. However, further investigation into other sperm-related genes is needed to establish their roles in male fertility.