title: Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells.
abstract: 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.
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Pan
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Shi
authors.affiliation: 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.|Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China.
authors.forename: Runsheng
authors.initials: R
authors.lastname: Li
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D049471:Pachytene Stage / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013090:Spermatocytes / Q000254:growth & development; D013091:Spermatogenesis / Q000235:genetics*; D013573:Synaptonemal Complex / Q000235:genetics; D013737:Testis / Q000254:growth & development / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C402397:Ndrg3 protein, mouse; D011506:Proteins