In Vitro Spermatogenesis; Past, Present, and Future

The study of culturing spermatogonial stem cells (SSCs) dates back to the 1950s. However, regeneration of complete spermatogenesis process in vitro is still a greater challenge. Studying spermatogenesis in vitro is significant in elucidating germ cell biology, and the knowledge may be useful for genetic manipulations of defective germ cells or producing transgenic animals, fertility preservation, and treatment of infertility. Fertility preservation would be more beneficial for adult and prepubescent patients who develop sterility due to gonadotoxins. Discovering of the stepwise stages in spermatogenesis and various forms of arrests at specific stages would help in the diagnosis of especially, idiopathic infertility and deciding treatment options. Different techniques have been tried to differentiate stem cells into germ cells over decades. A larger number of studies has used genetically manipulated stem cells to achieve differentiated germ cells. In contrast, differentiation of stem cells directly into SSCs bypassing the step into primordial germ cells (PGCs) to minimize time frame and employing techniques involved in least genetic manipulations are other important techniques to increase utilization within a clinical setting. As the use of transfected cell lines disqualifies the putative gametes obtained for clinical applications, trying to generate patient-specific germ cell with least genetic manipulations will be more effective in future applications, especially for patients with pre-pubertal cancer and azoospermic men who desire to become biological fathers.