Disruption of dmc1 Produces Abnormal Sperm in Medaka (Oryzias latipes).

Ji Chen,Zuoyan Zhu,Wei Hu,Kaiyao Huang,Daji Luo,Mengxi Cao,Hongling Hu,Xiaojuan Cui,Shaoting Jia,Yunsheng Zhang

doi:10.1038/srep30912

Abstract

DMC1 is a recombinase that is essential for meiotic synapsis. Experiments in extensive species of eukaryotes have indicated the independent role of DMC1 in repairing double strand breaks (DSBs) produced during meiosis I. Mutation of dmc1 in mice and human often leads to obstacles in spermatogenesis and male sterility. Here, we report on the disruption of dmc1 in male medaka (Oryzias latipes). Synapsis was disturbed in the mutant medaka testis nuclei, as observed in mice and other organisms. Unexpectedly, the mutant medaka could produce a few sperm and, although most of these had multiple tail or multiple head malformations, some of them could swim, and few of them even had insemination ability. Our transcriptome analysis showed that there was not a remarkable change in the expression of most of the genes involved in the pathways associated with the meiotic DNA repair and flagella assembly. Our results provided an indication of the accessory mechanisms that might be involved in the repair of DSBs during meiosis. In a species besides humans, we provided evidence that disorders in meiosis recombination might lead to the malformation of sperm.

Highlights

DMC1 is highly conserved in a wide range of eukaryotes[8]
Compared with the wild type (WT) medaka, there were no differences in growth or reproduction in the dmc1+/− hemizygotes
Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), we identified the apoptotic cells in the testes of the WT and dmc1−/− medaka

Summary

Introduction

DMC1 is highly conserved in a wide range of eukaryotes[8]. Experiments in mammals indicated that the mutation or deficiency of dmc[1] usually leads to defects in meiotic recombination, accompanied by the accumulation of double strand breaks (DSBs) and abnormal synaptonemal complex formation. The germ cells of dmc1−/− mice were arrested at meiosis I and no synaptonemal complexes were observed, the germ cells underwent apoptosis[9]. Studies of mutants of DMC1 (DMC1-m200v and DMC1-i137) showed that the mutated proteins were unable to combine the DNA strands steadily under physiological Mg2+ or Ca2+ conditions, and the patients were sterile[11,12]. These reports indicate that DMC1 is essential for the exchange of DNA strands between homologous chromosomes, as well as repairing DSBs during meiosis. Our results indicate that besides the introduction of aneuploidy, disruption to meiosis can induce malformations in the sperm

Methods

Results

Conclusion