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Abstract  Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete. During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome. Using mouse models with abrogated Y chromosome gene complements and Y-derived transgene we identified Y chromosome encoded  Zfy2  as the gene responsible for sperm formation and function. In the presence of a  Zfy2  transgene, mice lacking the Y chromosome and transgenic for two other Y-derived genes,  Sry  driving sex determination and  Eif2s3y  initiating spermatogenesis, are capable of producing sperm which when injected into the oocytes yield live offspring. Therefore, only three Y chromosome genes,  Sry ,  Eif2s3y  and  Zfy2 , constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Formation and Function in Assisted Fertilization