Sperm 28S ribosomal RNA fragments as a potential biomarker for embryo quality in in vitro fertilization

Male factors account for approximately 50% of infertility cases worldwide. However, the ability of current diagnostic tools-such as conventional semen analysis and sperm DNA fragmentation testing-to predict outcomes of assisted reproductive technology (ART) is limited.. Although sperm RNA content has emerged as a potential molecular marker of fertility, the role of microRNAs (miRNAs) and ribosomal RNA (rRNA) fragments in embryo development remains poorly understood.

We retrospectively analyzed 135 infertile couples who underwent IVF. Using quantitative RT‒PCR, we analyzed sperm samples and detected the expression of miR-150, miR-199a, miR-200a, miR-451, miR-181a, and ribosomal RNA (rRNA) fragments. These miRNAs were previously reported to be abundant in fertilized embryos and sperm but are expressed at low levels in oocytes.

We demonstrated the predominant presence of fragmented 28S rRNA, with significantly higher expression levels observed in patients who produced higher-quality embryos (7-9 blastomeres with < 10% fragmentation on day 3). Notably, 28S rRNA expression showed a strong positive correlation with embryo quality rates (P < 0.05), whereas no such association was detected for the 45S precursor, 18S, 5.8S rRNA forms and miRNAs. Importantly, conventional semen parameters (concentration and motility) were not significantly correlated with embryo quality, highlighting the unique predictive value of sperm rRNA profiling.

Our findings reveal that sperm 28S rRNA fragments may serve as novel biomarkers for predicting embryo developmental potential in IVF. These findings highlight the potential clinical utility of sperm RNA profiling in improving embryo selection and reproductive outcomes.