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1. C. M. Luetjens, E. Y. Xu, R. A. Rejo Pera, A. Kamischke, E. Nieschlag and J. Gromoll (2004) Association of meiotic arrest with lack of BOULE protein expression in infertile men. J Clin Endocrinol Metab 89(4): 1926-33.
Abstract Spermatogenesis is a complex developmental process of mitotic and meiotic cell divisions that ultimately results in production of haploid spermatozoa. Recent studies in flies demonstrate that the BOULE gene encodes a key factor of meiosis in male germ cells, regulating the expression of twine, a cdc25 phosphatase, which promotes progression through meiosis. In this study, we investigated whether a common mechanism underlies the block of germ cell maturation observed in idiopathic and nonidiopathic azoospermic patients with meiotic arrest. We examined, by immunohistochemistry, BOULE and CDC25A phosphatase protein, the human homolog of twine, expression in 47 men with meiotic arrest, mixed atrophy, or normal spermatogenesis. The presence of genetic alterations within the BOULE gene was investigated by single-stranded conformation polymorphism. BOULE protein expression in men with complete spermatogenesis can be restricted to stages from leptotene up to stages of late spermatocytes, whereas CDC25A expression ranges from leptotene spermatocytes to elongating spermatids. Although spermatocytes were present in all testicular biopsies with meiotic arrest (28 testes), BOULE protein expression was completely lacking. In addition, in nearly all biopsies in which BOULE was absent, CDC25A was concomitantly lacking. However, no mutations or polymorphisms in the BOULE gene were identified, which could explain the lack of BOULE or CDC25A expression. These results indicate that a major group of infertile men with meiotic arrest lack BOULE protein and its putative target, CDC25A expression. The spermatogenic failure seems to arise from factor(s) upstream of BOULE, which are possibly involved in regulating transcription and/or translation of BOULE. Thus, the spermatogenic damage leading to meiotic arrest is independent of the etiology and indicates that BOULE is a possible fundamental mediator of meiotic transition in the human. PMID: [15070965]
2. E. Kostova, C. H. Yeung, C. M. Luetjens, M. Brune, E. Nieschlag and J. Gromoll (2007) Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men. Mol Hum Reprod 13(2): 85-93.
Abstract
The complex process of spermatogenesis requires the expression and precise coordination of a multitude of genes. Abnormal function of such genes is frequently associated with male infertility. Among these candidates is the human BOULE gene that is a possible fundamental mediator of meiotic transition. In this study, we describe for the first time the existence of three BOULE transcript variants (B1, B2 and B3). We investigated their tissue specificity and mRNA transcript levels in 23 testis biopsies from infertile men. B1, B2 and B3 differed solely in their N-terminal sequences, which are encoded by three alternatively spliced exons 1. In humans, all three isoforms are exclusively expressed in the testes in a relative proportion of 80 PMID: [17114206]
3. Y. M. Lin, P. L. Kuo, Y. H. Lin, Y. N. Teng and J. S. Nan Lin (2005) Messenger RNA transcripts of the meiotic regulator BOULE in the testis of azoospermic men and their application in predicting the success of sperm retrieval. Hum Reprod 20(3): 782-8.
4. Y. M. Lin, C. L. Chung and Y. S. Cheng (2009) Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis. J Clin Endocrinol Metab 94(7): 2650-7.
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Ref: C. M. Luetjens, E. Y. Xu, R. A. Rejo Pera, A. Kamischke, E. Nieschlag and J. Gromoll (2004) Association of meiotic arrest with lack of BOULE protein expression in infertile men. J Clin Endocrinol Metab 89(4): 1926-33. PMID: [15070965] |
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Ref: E. Kostova, C. H. Yeung, C. M. Luetjens, M. Brune, E. Nieschlag and J. Gromoll (2007) Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men. Mol Hum Reprod 13(2): 85-93. PMID: [17114206] |
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Ref: Y. M. Lin, C. L. Chung and Y. S. Cheng (2009) Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis. J Clin Endocrinol Metab 94(7): 2650-7. PMID: [19417033] |
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