Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

Abstract

Gametogenetin (GGN) binding protein 2 (GGNBP2) is a zinc finger protein expressed abundantly in spermatocytes and spermatids. We previously discovered that Ggnbp2 resection caused metamorphotic defects during spermatid differentiation and resulted in an absence of mature spermatozoa in mice. However, whether GGNBP2 affects meiotic progression of spermatocytes remains to be established. In this study, flow cytometric analyses showed a decrease in haploid, while an increase in tetraploid spermatogenic cells in both 30‐ and 60‐day‐old Ggnbp2 knockout testes. In spread spermatocyte nuclei, Ggnbp2 loss increased DNA double‐strand breaks (DSB), compromised DSB repair and reduced crossovers. Further investigations demonstrated that GGNBP2 co‐immunoprecipitated with a testis‐enriched protein GGN1. Immunofluorescent staining revealed that both GGNBP2 and GGN1 had the same subcellular localizations in spermatocyte, spermatid and spermatozoa. Ggnbp2 loss suppressed Ggn expression and nuclear accumulation. Furthermore, deletion of either Ggnbp2 or Ggn in GC‐2spd cells inhibited their differentiation into haploid cells in vitro. Overexpression of Ggnbp2 in Ggnbp2 null but not in Ggn null GC‐2spd cells partially rescued the defect coinciding with a restoration of Ggn expression. Together, these data suggest that GGNBP2, likely mediated by its interaction with GGN1, plays a role in DSB repair during meiotic progression of spermatocytes.

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

“…Members of these two gene families play pivotal roles in holding sister chromatids together or segregation, chromosome condensation, DNA double-strand breaks repairing as well as linking homologous chromosomes 54–59. In addition, the decrease of Ggnbp2 expression could have also negatively affected spermatogenesis since Ggnbp2 encodes a protein that is essential in DNA double-strand breaks repairing during meiotic progression of spermatocytes 60. The dysregulation of testicular gene expression could also lead to impaired sperm motility.…”

“…[54][55][56][57][58][59] In addition, the decrease of Ggnbp2 expression could have also negatively affected spermatogenesis since Ggnbp2 encodes a protein that is essential in DNA double-strand breaks repairing during meiotic progression of spermatocytes. 60 The dysregulation of testicular gene expression could also lead to impaired sperm motility. Accordingly, RNA-sequencing and subsequent real-time PCR-validation revealed significant drop in the expression of some mitochondrial genes, including MT-ND1, MT-ND2, MT-ND4, MT-ND5 and MT-ND4L, all of which encode the core subunits of mitochondrial membrane respiratory chain, NADH dehydrogenase (complex I), 61 that is essential for oxidative phosphorylation and sperm motility.…”

Effects of gametogenetin‐binding protein 2 on proliferation, invasion and migration of prostate cancer PC‐3 cells

“…GGNBP2 is closely related to spermatogenesis. As a testis‐specific protein, it is first expressed in the late stage of spermatocytes and the early stage of round spermatids, with maximum in the early stage of spermatid meiosis (Guo et al, ). Recently, GGNBP2 protein has been reported to be down‐regulated in breast cancer tissue compared with in normal breast tissue, suggesting that GGNBP2 may function as a tumour suppressor gene in breast cancer (Lan et al, ).…”

Genome-Wide Allele-Specific Expression in Obligately AsexualDaphnia pulexand the Implications for the Genetic Basis of Asexuality

“…During mouse oocyte development, the loss of RanBP2 leads to abnormal chromosome segregation during anaphase I ( Kim et al 2017 ). Ggnbp2 is a zinc-finger protein expressed abundantly in spermatocytes and spermatids in mice, loss of which affects prophase I and inhibits the formation of haploid cells in vitro ( Guo et al 2018 ). Finally, Wee1 is a universal mitotic inhibitor, known to be down-regulated during oogenesis in Xenopus , with ectopic expression in immature oocytes leading to failure to enter meiosis II ( Nakajo et al 2000 ).…”