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The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found  Ndrg3 , a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of  Ndrg3  was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of  Ndrg3  gene led to sub-infertility during the male early maturation. In the  Ndrg3  +/−  germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells  in vitro . Deficiency of  Ndrg3  gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that  Ndrg3  gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse.

Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells