Presence of Very Small Embryonic-Like Stem Cells (VSELs) in human semen samples; A novel finding

Presence of Very Small Embryonic-Like Stem Cells (VSELs) in human semen samples; A novel finding Background: The presence of a very small, quiescent, and pluripotent population of stem cells termed as “VSELs” was first reported in 2006. Those cells have observed in various organs in the mammalian body including bone marrow, peripheral blood, endometrium, ovary and testis so on. But their existence in seminal plasma has not been reported so far. The aim of the present study was to find out whether VSELs are present in human semen samples and if so, study their characteristics and relationship with semen parameters. Semen samples were collected from sub fertile men and analyzed according to WHO guidelines. VSELs in seminal plasma were detected using Giemsa stain. The presence of cells with primitive germ cell properties was confirmed by GPR125 expression and alkaline phosphatase activity. Results: A very small and round cell population, notably smaller than spermatids was observed in all semen samples. The mean (SD) size of cells was 5.1 (0.1) ranging from 3.16 - 6.8 µm, and exhibited a large centrally located nucleus, resulting in a high nucleus-to-cytoplasm (N/C) ratio of 1.75 (0.3). The mean (SEM) concentration of VSELs was 17.21 (4.42) m/ml. VSELs count was significantly high in oligozoospermics compared to normozoospermics (22.71 (5.89) vs 6.22 (1.81), p < 0.05) respectively. There was a positive correlation between VSEL and immature germ cells (r = 0.759, p < 0.001). Two distinct populations of cells were identified according to their color intensity; VSEL dark and pale, 53% and 47% respectively. Minor percentages of sub-populations positive for alkaline phosphatase activity (6.06%) and expressing GPR 125 (5.56%) were also observed. Very slow rate of propagation (3%) and the ability to make embryoid bodies were exhibited by the isolated cells cultured for five weeks. Conclusions: To the best of our knowledge this is the first report on the presence of VSELs in semen samples. Sub-population of cells with primitive germ cell properties would be a good source of stem cells for future studies on in vitro spermatogenesis.