An azoospermic man with a double-strand DNA break-processing deficiency in the spermatocyte nuclei: Case report

• Published in: Human reproduction (Oxford) Vol. 21; no. 5; pp. 1194 - 1203
• Main Authors: Sciurano, R.B., Rahn, M.I., Pigozzi, M.I., Olmedo, S. Brugo, Solari, Alberto J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2006; Oxford Publishing Limited (England)
• Subjects: Adaptor Proteins, Signal Transducing; Adenosine Triphosphatases - genetics; Adult; asynapsis; Ataxia Telangiectasia Mutated Proteins; azoospermia; Biological and medical sciences; BRCA1 Protein - analysis; Carrier Proteins; Cell Cycle Proteins - analysis; Cell Cycle Proteins - genetics; Cell Nucleus - chemistry; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Chromosome Pairing - genetics; DNA - metabolism; DNA Damage - genetics; DNA Repair; DNA-Binding Proteins - analysis; DNA-Binding Proteins - genetics; double-strand DNA breaks; Endodeoxyribonucleases; Esterases - genetics; Gynecology. Andrology. Obstetrics; Histones - analysis; Humans; Male; Medical sciences; Meiosis - genetics; meiotic arrest; Mutation; MutL Protein Homolog 1; Nuclear Proteins - analysis; Nuclear Proteins - genetics; Oligospermia - genetics; Oligospermia - metabolism; Protein-Serine-Threonine Kinases - analysis; Rad51 Recombinase - analysis; Spermatocytes - chemistry; Spermatocytes - metabolism; Spermatocytes - ultrastructure; Spermatogenesis - genetics; SPO11; Synaptonemal Complex - chemistry; Synaptonemal Complex - genetics; Synaptonemal Complex - metabolism; Testis - pathology; Tumor Suppressor Proteins - analysis; asynapsis; double-strand DNA breaks; meiotic arrest; azoospermia; SPO11; Human; Deficiency; Break; Male; Germinal cell; Case study; Vertebrata; Azoospermia; Double stranded DNA; Mammalia; Spermatocyte; Male sterility; Male genital diseases
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dei479

BACKGROUND: The mechanisms of meiotic arrest in human spermatogenesis are poorly known. METHODS AND 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 γ-H2AX, abnormal presence of BRCA1 among autosomal axes, absence of RAD51 in early and advanced spermatocytes and permanence of γ-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.