Generation of functional spermatids from azoospermia patients is of unusual significance for treating male infertility. Here we show an efficient approach to obtain human functional haploid spermatids from cryptorchid patients. Cryptorchid patients had normal chromosome karyotype and excluded Y chromosome microdeletion. Expression of numerous markers for meiotic male germ cells and haploid cells was up-regulated in human spermatogonial stem cells (SSCs) of cryptorchidism patients by retinoic acid (RA) and stem cell factor (SCF) treatment. Meiotic spreads revealed that RA and SCF resulted in a higher percentage of SCP3-and CREST- positive cells in human SSCs. DNA content analyses showed that RA and SCF induced an obvious increase of haploid cells. Notably, haploid spermatids generated from human SSCs of cryptorchid patients could fertilize mouse oocytes to form embryos that developed into 8-cell stages. This study thus provides an invaluable source of autologous male gametes for treating male infertility of azoospermia patients.
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