An azoospermic man with a double-strand DNA break-processing deficiency in the spermatocyte nuclei: case report.
BACKGROUND
The mechanisms of meiotic arrest in human spermatogenesis are poorly known.


RESULTS
A testicular biopsy from an azoospermic male showed complete spermatogenesis arrest at the spermatocyte stage, asynapsis, lack of formation of the XY body, partial reversion to a mitotic-like division and cell degeneration both at the prophase and at the abnormal cell divisions. Synaptonemal complex analysis showed minor segments of synapsis and mainly single axes. Fluorescent immunolocalization of meiotic proteins showed normal SYCP3, scarcity of SYCP1, null MLH1 foci, about 10 patches of gamma-H2AX, abnormal presence of BRCA1 among autosomal axes, absence of RAD51 in early and advanced spermatocytes and permanence of gamma-H2AX labelling up to the abnormal spermatocyte divisions that are the most advanced stage reached. There are at least six dominions of evenly packed chromatin resembling that of the normal XY body, but no true XY body.


CONCLUSIONS
The protein phenotype and the fine structure of the nuclei are compatible with a deficiency of the processing of double-strand DNA breaks in the zygotene-like spermatocytes, but the features of this defect do not agree with Spo11, Sycp1, Atm and Dmc1 null mutations, which give absence of XY body, synapsis disturbances and spermatocyte apoptosis in mice.
Facultad de Medicina, Centro de Investigaciones en Reproducción (CIR), Buenos Aires, Argentina.
R B
RB
Sciurano
M I
MI
Rahn
M I
MI
Pigozzi
S Brugo
SB
Olmedo
Alberto J
AJ
Solari
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000032:analysis; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D023902:Chromosome Pairing / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000235:genetics; D006657:Histones / Q000032:analysis; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D009845:Oligospermia / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D051135:Rad51 Recombinase / Q000032:analysis; D013090:Spermatocytes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D013091:Spermatogenesis / Q000235:genetics; D013573:Synaptonemal Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000032:analysis; D000099257:Meiotic Recombination Protein SPO11
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D006657:Histones; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; D025521:Tumor Suppressor Proteins; D000099257:Meiotic Recombination Protein SPO11; C468783:H2AX protein, human; C501486:MLH1 protein, human; C489753:SYCP1 protein, human; C490060:SYCP3 protein, human; C576324:ATM protein, human; C576325:Atm protein, mouse; C074556:DMC1 protein, human