Differential protein expression profiles in human sperm from teratozoospermic and normozoospermic men identify LTBP1 and TGF-βR1 as potential biomarkers within the TGF-β signalling pathway

Among cases of infertility, up to 50% are attributed to male infertility factors. Male infertility is associated with alterations in sperm proteins that are essential for normal sperm function. Alterations in proteins within the transforming growth factor-beta (TGF-β) signalling pathway are linked with several types of male infertility. However, the underlying mechanisms remain unclear. In this study, we proposed to use proteomic analysis to identify the proteomic profile in human sperm from normozoospermic (NOR) and teratozoospermic (TER) men. The results indicated 39 overlapping proteins associated with the TGF-β signalling pathway. Six proteins that were differentially expressed and had a log2 fold change of ≥ 1 or ≤ -1 were considered to be the differentially expressed proteins in human sperm between the groups. Among these proteins, the latent-transforming growth factor beta-binding protein 1 (LTBP1) was significantly increased in the TER group compared to the NOR group. Immunocytochemistry revealed that the protein expression of TGF-β receptor type 1 (TGF-βR1) was localised in the human sperm head. It was also significantly increased in the TER group. Validation analysis revealed that the mRNA expression levels of LTBP1 and TGFBR1 genes were significantly upregulated in the TER group relative to the NOR group. Interestingly, an increase in LTBP1 and TGF-βR1 protein expression was correlated with a decrease in the percentage of normal sperm morphology. Our findings, for the first time, demonstrate a significant association between the expression of LTBP1 and TGF-βR1 and abnormal sperm morphology, supporting their consideration as novel exploratory biomarkers for further investigation in infertility, especially in TER men.