GEMC1 and CCNO are required for efferent duct development and male fertility

GEMC1 is a Geminin family protein that triggers the E2F4/5-mediated transcriptional activation of target genes, including many required for multiciliogenesis, such as Mcidas, FoxJ1 and Ccno. Male mice lacking either Gemc1 or Ccno were found to be infertile, but the origin of this defect has remained unclear. Here we show that mice lacking either Gemc1 or Ccno showed a nearly empty seminiferous tubule phenotype. While both genes were expressed in the testes, much higher levels were observed in the efferent ducts that mobilize sperm to the epididymis. We found that both GEMC1 and CCNO were required for the generation of multiciliated cells in the efferent ducts but that they differentially affect activation of FoxJ1 and Tp73. These data indicate that defective efferent duct development, rather than defects in testes development, are likely the primary origin of male infertility observed in the absence of GEMC1 and CCNO and this could extend to Reduced Generation of Multiple Motile Cilia patients with MCIDAS and CCNO mutations.\n\nSummary statementWe demonstrate that male mice lacking GEMC1 or CCNO are infertile due to defects in the formation of the efferent ducts.