Presence of Very Small Embryonic-Like Stem Cells in Human Semen Samples: A Novel Finding

Introduction: A very small, quiescent, and pluripotent population of stem cells termed very small embryonic-like stem cells (VSELs) has been reported in various organs. However, their presence in seminal plasma has not yet been reported. Aims: This study aimed to determine whether VSELs are present in human semen samples and, if so, to study their characteristics. Methods: VSELs in seminal plasma were sought using Giemsa staining. The primitive germ cell properties were confirmed by G protein-coupled receptor A3 (GPR125) expression and alkaline phosphatase (ALP) activity. Results: A very small, round cell population, notably smaller than spermatids, was observed in all semen samples. The mean (± SD) size of these cells was 5.1 ± 0.1 [Formula: see text]m, and the cells presented a large, centrally located nucleus, resulting in a high nucleus-cytoplasm (N/C) ratio of 1.75 ± 0.3. The mean (± SEM) concentration of VSELs was 17.21 ± 4.42 m/mL. The VSEL count was significantly higher in oligozoospermic individuals compared to normozoospermic controls (22.71 ± 5.89 vs. 6.22 ± 1.81; [Formula: see text] < 0.05). There was a positive correlation between the number of VSELs and immature germ cells ([Formula: see text] = 0.759, [Formula: see text] < 0.001). Two distinct populations of cells were identified; 53% and 47% of VSELs were dark and pale, respectively. Minor percentages of subpopulations positive for ALP activity (6.06%) and expressing GPR125 (5.56%) were also observed. A very slow rate of propagation (3%) and the ability to form small embryoid bodies were exhibited by the isolated cells cultured for 5 weeks. Conclusion: A subpopulation of cells with primitive germ cell properties would be a good source of stem cells for future studies on in vitro spermatogenesis.