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However, mice mutant for WNT signalling effector <jats:italic>\u03b2<\/jats:italic>-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the <jats:italic>Gpr177<\/jats:italic> gene (the mouse orthologue of <jats:italic>Drosophila Wntless<\/jats:italic>), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the <jats:italic>Gpr177<\/jats:italic> gene was conditionally depleted in germ cells (<jats:italic>Gpr177<\/jats:italic><jats:sup>flox\/flox<\/jats:sup>, <jats:italic>Mvh<\/jats:italic>-Cre; <jats:italic>Gpr177<\/jats:italic><jats:sup>flox\/flox<\/jats:sup>, <jats:italic>Stra8<\/jats:italic>-Cre) and Sertoli cells (<jats:italic>Gpr177<\/jats:italic><jats:sup>flox\/flox<\/jats:sup>, <jats:italic>Amh<\/jats:italic>-Cre). No obvious defects in fertility and spermatogenesis were observed in these three <jats:italic>Gpr177<\/jats:italic> conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific <jats:italic>Gpr177<\/jats:italic> deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8-month-old <jats:italic>Gpr177<\/jats:italic><jats:sup>flox\/flox<\/jats:sup>, <jats:italic>Amh<\/jats:italic>-Cre mice. Elevation of reactive oxygen species (ROS) was detected in <jats:italic>Gpr177<\/jats:italic> cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific <jats:italic>Gpr177<\/jats:italic> knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis.<\/jats:p>","DOI":"10.1038\/cddis.2016.191","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T13:05:05Z","timestamp":1467291905000},"page":"e2281-e2281","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Does murine spermatogenesis require WNT signalling? 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