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Mol. Hum. Reprod. Advance Access originally published online on November 17, 2006
Molecular Human Reproduction 2007 13(2):85-93; doi:10.1093/molehr/gal101
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men

E. Kostova, C.H. Yeung, C.M. Luetjens, M. Brune, E. Nieschlag and J. Gromoll1

Institute of Reproductive Medicine of the University, Domagkstrasse, Muenster, Germany

1 To whom correspondence should be addressed at: Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48149 Muenster, Germany. E-mail: joerg.gromoll{at}ukmuenster.de


   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 80:220:1 for B1, B2 and B3, respectively. RT–PCR quantification revealed significantly reduced mRNA expression of all three variants in testicular biopsies with meiotic arrest (MA) compared with those with qualitatively complete spermatogenesis. Alteration of the B1/B2 and B1/B3 transcript ratios was correlated with reduced meiotic capacity of spermatocytes to produce round spermatids as assessed by flow cytometry. Furthermore, BOULE mRNA reduction in biopsies with MA paralleled the absence of BOULE protein as analysed by immunohistochemistry. In conclusion, the relative proportions of B1, B2 and B3 may serve as predictive markers for meiotic efficiency and thus the probability of finding haploid cells in the human testis. Among the three isoforms, B2 might have the major role for meiotic completion.

Key words: BOULE/isoforms/meiotic arrest/mRNA quantification


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