PRJDB5382 Oocyte depletion in Sry-mutated XY female mice Little is known about the mechanisms underlying infertility in male to female sex reversal females. To gain a better understanding of germ cells dysfunction in this condition, we produced XY females via the CRISPR/Cas9 system in C57BL/6 inbred strain mice. Mutant mice showed severe attrition of germ cells during foetal development, resulting in depletion of ovarian germ cells before sexual maturation. Comprehensive transcriptome analysis of embryonic day 13.5 primordial germ cells (PGCs) and postnatal day 1 oocytes demonstrated that XY PGCs had already deviated from the developmental process at the mitotic stage. Furthermore, this grievous disruption, which caused germ cell deterioration in XY females, was shown to proceed from the germ cells themselves. These results provide novel insight into the germ cell depletion of sex reversal mice as well as into disorders of sex differentiation in human, such as Swyer syndrome, wherein patients present as typical females albeit with an XY karyotype and infertile. Oocyte depletion in Sry-mutated XY female mice bioproject PRJDB5382 PRJDB5382 true Little is known about the mechanisms underlying infertility in male to female sex reversal females. To gain a better understanding of germ cells dysfunction in this condition, we produced XY females via the CRISPR/Cas9 system in C57BL/6 inbred strain mice. Mutant mice showed severe attrition of germ cells during foetal development, resulting in depletion of ovarian germ cells before sexual maturation. Comprehensive transcriptome analysis of embryonic day 13.5 primordial germ cells (PGCs) and postnatal day 1 oocytes demonstrated that XY PGCs had already deviated from the developmental process at the mitotic stage. Furthermore, this grievous disruption, which caused germ cell deterioration in XY females, was shown to proceed from the germ cells themselves. These results provide novel insight into the germ cell depletion of sex reversal mice as well as into disorders of sex differentiation in human, such as Swyer syndrome, wherein patients present as typical females albeit with an XY karyotype and infertile.