Sperm-borne mRNAs as a biomarker for human sperm quality

Although the World Health Organization (WHO) criteria for semen quality are widely followed, a significant proportion of sperm samples provided by sperm banks around the world fail to lead to successful pregnancies, highlighting the needs for better biomarkers that allow for identification of truly fertile sperm. Laboratory study using human sperm samples. We profiled and compared mRNAs in sperm samples with higher (5 pregnancies out of <20 attempts, >25%; n=10) and lower (<1 pregnancy out of 30 attempts, <3.3%; n=10) pregnancy rates using RNA-Seq. Among numerous differentially expressed genes (DEGs) identified between sperm with high (HPR) and low (LPR) pregnancy rates. We selected 23 spermatogenesis-related genes and 10 energy metabolic genes as potential biomarkers for sperm quality because these showed the greatest difference in abundance in the two groups. Further optimization by examining their expression levels in 30 HPR and 30 LPR sperm yielded a list of 9 genes that were selected as biomarkers because they could distinguish sperm samples with extremely high (>40%) or extremely low (<1%) pregnancy rates. We then re-tested all of the 60 samples in a blinded manner (i.e., no sample information provided to the examiner) and our results showed that these 9 genes can reliably distinguish the two extreme groups. Our data suggest that sperm-borne mRNAs can be excellent biomarkers for predicting the fertility potential of sperm in addition to the current motility- and morphology-based methods. We are exploring other RNA species as well as epigenetic markers as potential biomarkers for human sperm quality.