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Hum. Reprod. Advance Access originally published online on February 23, 2006
Human Reproduction 2006 21(7):1749-1758; doi:10.1093/humrep/del051
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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

Chromosome constitution and apoptosis of immature germ cells present in sperm of two 47,XYY infertile males

J.P. Milazzo, N. Rives 1 , N. Mousset-Siméon and B. Macé

Reproductive Biology Laboratory – CECOS, Rouen University Hospital, Rouen, France

1 To whom correspondence should be addressed at: Docteur Nathalie Rives, Reproductive Biology Laboratory – CECOS, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France. E-mail: nathalie.rives{at}chu-rouen.fr

BACKGROUND: In order to assess sperm alterations observed in some XYY males, we analysed the chromosome constitution as well as apoptosis expression in germ cells from two oligozoospermic males with high count of immature germ cells in their semen. METHODS: Sex chromosome number and distribution were assessed at pachytene stage by fluorescence in situ hybridization (FISH). Immature germ cells and spermatozoa were examined by FISH and TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end (TUNEL) assay, combined with immunocytochemistry using the proacrosin-specific monoclonal antibody (mAb 4D4). RESULTS: For patients 1 and 2, two Y chromosomes were present in respectively 60.0 and 39.6% of pachytenes. The three sex chromosomes were always in close proximity and partially or totally condensed in a sex body. XYY spermatocytes I escape the pachytene checkpoint and achieve meiosis. Nevertheless, nuclear division and/or cytokinesis were often impaired during meiosis leading to diploid (mainly 47,XYY cells) and tetraploid (94,XXYYYY) meiocytes. The presence of binucleated (23,Y)(24,XY) immature germ cells resulting from cytokinesis failure agree with a preferential segregation of the two Y chromosomes during meiosis I. In addition, 69.6% (patient 1) and 53.12% (patient 2) of post-reductional round germ cells were XY. However, high level of apoptotic round germ cells (94.9% for patient 1 and 93.3% for patient 2) was detected and may explain the moderate increase of hyperhaploid XY spermatozoa. Segregation errors also occurred in the XY cell line responsible for disomic 18 and X, as well as 46,XY diploid spermatozoa. CONCLUSIONS: Our data are in agreement with the persistence of the extra Y chromosome during meiosis in XYY oligozoospermic males responsible for spermatogenesis impairment and a probable elimination via apoptosis of most XYY germ cells not solely during but also after meiosis.

Key words: apoptosis/chromosome anomalies/immature germ cells/meiotic disorders/XYY males


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E. C. Wong, K. A Ferguson, V. Chow, and S. Ma
Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male
Hum. Reprod., February 1, 2008; 23(2): 374 - 378.
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