Journal: The New England journal of medicine

X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men.

Librarian's Comment : The molecular pathophysiology of spermatogenic failure remains obscure in the majority of infertile men suffering from non-obstructive azoospermia. Here, Yatsenko et al. dissect the role of testisexpressed 11 gene (TEX11) on chromosome Xq13.2 in human spermatogenesis. In contrast to normozoospermic men, novel TEX11 mutations were detected in patients with azoospermia and could be assigned to a meiotic arrest of spermatogenesis resembling the phenotype of Tex11-deficient male mice. At the protein level, testicular tissue obtained from azoospermic men with TEX11 mutations and meiotic arrest lacked TEX11 expression, which is found in late spermatocytes as well as round and elongated spermatids in normal human testes
Published in : The New England journal of medicine
Authors : Yatsenko AN, Georgiadis AP, Röpke A, Berman AJ, Jaffe T, Olszewska M, Westernströer B, Sanfilippo J, Kurpisz M, Rajkovic A, Yatsenko SA, Kliesch S, Schlatt S, Tüttelmann F

Abstract : BACKGROUND: The genetic basis of nonobstructive azoospermia is unknown in the majority of infertile men. METHODS: We performed array comparative genomic hybridization testing in blood samples obtained from 15 patients with azoospermia, and we performed mutation screening by means of direct Sanger sequencing of the testis-expressed 11 gene (TEX11) open reading frame in blood and semen samples obtained from 289 patients with azoospermia and 384 controls. RESULTS: We identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved three TEX11 exons. This loss, which was identical in 2 patients with azoospermia, predicts a deletion of 79 amino acids within the meiosis-specific sporulation domain SPO22. Our subsequent mutation screening showed five novel TEX11 mutations: three splicing mutations and two missense mutations. These mutations, which occurred in 7 of 289 men with azoospermia (2.4%), were absent in 384 controls with normal sperm concentrations (P=0.003). Notably, five of those TEX11 mutations were detected in 33 patients (15%) with azoospermia who received a diagnosis of azoospermia with meiotic arrest. Meiotic arrest in these patients resembled the phenotype of Tex11-deficient male mice. Immunohistochemical analysis showed specific cytoplasmic TEX11 expression in late spermatocytes, as well as in round and elongated spermatids, in normal human testes. In contrast, testes of patients who had azoospermia with TEX11 mutations had meiotic arrest and lacked TEX11 expression. CONCLUSIONS: In our study, hemizygous TEX11 mutations were a common cause of meiotic arrest and azoospermia in infertile men. (Funded by the National Institutes of Health and others.).

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