Zahra Bakhtiary

Seminal extracellular vesicles (SemEVs) are repositories of biomolecules, including metabolites involved in the regulation of sperm function. The correlation between the metabolite profile of SemEVs and semen parameters, along with their role in regulating sperm function, is an unexplored area. This preliminary study evaluated the metabolomic content of SemEVs. Semen samples were obtained from 18 healthy men, and SemEVs were extracted from seminal plasma using the size exclusion chromatography qEV Gen 2–35 nm column coupled with an automatic fraction collector. The physical characterization of SemEVs was carried out with the ZetaView PMX-430-Z QUATT laser system. EV protein markers were detected using Western blot. In addition, these SemEVs were used for metabolomic profiling and functional bioinformatic analysis. The mean concentration of isolated SemEVs was 1.7 ± 1.1 × 10¹¹/mL of seminal plasma, whereas SemEVs size and zeta potential were 129.5 ± 5.5 nm and −40.03 ± 3.99 mV, respectively. Western blot analysis confirmed the presence of EV specific markers such as CD81, ALIX, and TSG101. A total of 107 metabolites were identified using this untargeted metabolomic approach in SemEVs. Bioinformatics analysis further revealed that metabolites associated with tyrosine metabolism were highly enriched in these SemEVs. Ingenuity Pathway Analysis (IPA) also indicated that these metabolites present in SemEVs were involved in the regulation of the free radical scavenging pathway. Furthermore, our metabolomic results suggest that these SemEV-associated metabolites may play a pivotal role in the maintenance of seminal plasma redox homeostasis.

Infertility is a prevalent global issue affecting approximately 17.5% of adults, with sole male factor contributing to 20–30% of cases. Oxidative stress (OS) is a critical factor in male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants. This imbalance detrimentally affects sperm function and viability, ultimately impairing fertility. OS also triggers molecular changes in sperm, including DNA damage, lipid peroxidation, and alterations in protein expression, further compromising sperm functionality and potential fertilization. Diagnostic tools discussed in this review offer insights into OS markers, antioxidant levels, and intracellular ROS concentrations. By accurately assessing these parameters, clinicians can diagnose male infertility more effectively and thus tailor treatment plans to individual patients. Additionally, this review explores various treatment options for males with OS-associated infertility, such as empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. By addressing the root causes of male infertility and implementing targeted interventions, clinicians can optimize treatment outcomes and enhance the chances of conception for couples struggling with infertility.