Serum expression signature of TUG1, MALAT1, miR-483, and miR-141 and their targets TGF-β1 and STAT3 in severe male factor infertility

Long non-coding RNAs and microRNAs have evolved as biomarkers and specific therapeutic targets for male infertility. We investigated the seminal plasma and serum expression profiles of TUG1, MALAT1, miR-483, and miR-141 and their targets TGF-β1 and STAT3 in severe male factor infertility. The potential of their serum levels as minimally invasive, clinically accessible, and more feasible biomarkers and their clinical correlations were explored. Thirty non-obstructive azoospermia (NOA) patients, 30 severe oligozoospermia (SO) patients, and 30 healthy fertile men (controls) were enrolled. Compared to controls, seminal plasma and serum TUG1 and miR-141 were downregulated; meanwhile, miR-483 and STAT3 were upregulated in both NOA and SO patients, while MALAT1 was upregulated in NOA but downregulated in SO patients. Seminal plasma TGF-β1 was higher in NOA patients than in controls and SO patients, while its serum levels were not statistically different between the studied groups. NOA patients showcased higher serum STAT3 mRNA expression than SO patients. Seminal plasma and serum levels of most of the tested markers were correlated among NOA and SO patients. Multivariate logistic analysis unraveled the association of serum TUG1 and miR-141 with NOA risk and serum TUG1 and miR-483 with SO risk. A serum-based panel of TUG1/miR-141 and TUG1/miR-483 discriminated NOA (AUC = 0.93) and SO (AUC = 0.972) from controls, respectively. Serum miR-141 was correlated with the hormonal profile in NOA patients. In SO patients, serum TUG1 was correlated with total testosterone levels and abnormal sperm motility, while serum MALAT1 was inversely correlated with the testicular volume. Conclusively, this study introduces a novel serum-based prediction panel of TUG1/miR-141 and TUG1/miR-483 to help enhance the accuracy of NOA and SO diagnosis. Serum MALAT1 and STAT3 could be useful in stratifying NOA and SO. These findings warrant more future investigations for their possible implication in male infertility diagnostics.