• PMID: 28290521
• Gene Name: NDRG3
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

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

Pan H, Zhang X, Jiang H, Jiang X, Wang L, Qi Q, Bi Y, Wang J, Shi Q, Li R.

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. FAU - Pan, Hongjie AU - Pan H AD - WHO Collaborating Center for Research in Human Reproduction, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China. AD - Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China. FAU - Zhang, Xuan AU - Zhang X AD - WHO Collaborating Center for Research in Human Reproduction, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China. AD - Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China. FAU - Jiang, Hanwei AU - Jiang H AD - Laboratory of Molecular and Cell Genetics, CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science &Technology of China, Hefei, 230027, China. FAU - Jiang, Xiaohua AU - Jiang X AD - Laboratory of Molecular and Cell Genetics, CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science &Technology of China, Hefei, 230027, China. FAU - Wang, Liu AU - Wang L AD - Laboratory of Molecular and Cell Genetics, CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science &Technology of China, Hefei, 230027, China. FAU - Qi, Qi AU - Qi Q AD - WHO Collaborating Center for Research in Human Reproduction, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China. AD - Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China. FAU - Bi, Yuan AU - Bi Y AD - WHO Collaborating Center for Research in Human Reproduction, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China. AD - Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China. FAU - Wang, Jian AU - Wang J AD - WHO Collaborating Center for Research in Human Reproduction, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China. AD - Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China. FAU - Shi, Qinghua AU - Shi Q AD - Laboratory of Molecular and Cell Genetics, CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science &Technology of China, Hefei, 230027, China.