Hum. Reprod. Advance Access published online on April 11, 2007
Human Reproduction, doi:10.1093/humrep/dem045
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Meiotic abnormalities in patients bearing complete AZFc deletion of Y chromosome
1 Laboratoire de Biologie de la Reproduction, Hôpital de la Conception, 147 Bd Baille, 13385 Marseille cedex 05, France 2 Laboratoire Biologie de la Reproduction, Hôpital Nord, 42055 Saint Etienne, France 3 Laboratoire de Biogénotoxicologie et Mutagenèse Environnementale (EA 1784), IFR PMSE 112, Faculté de Médecine Timone, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France
4 To whom correspondence should be addressed at: Laboratoire de Biologie de la Reproduction, Hôpital de la Conception, 147 Bd Baille, 13385 Marseille cedex 05, France. E-mail: mguichaoua{at}ap-hm.fr
BACKGROUND: We studied meiosis in three infertile patients presenting complete AZFc microdeletion and three controls.
METHODS: Primary spermatocytes were immunolabeled with SCP3, BRCA1 and 
H2AX. We quantified the leptotene, zygotene and pachytene stages, and pachytene abnormalities: asynapsis and fragmented and dotted synaptonemal complexes (SCs).
RESULTS: SCP3 level was significantly higher in leptotene and zygotene (bouquet) stages in patients, suggesting AZFc may have a direct effect on early prophase. SCs were abnormal in 77.3% of pachytene nuclei of patients versus 30.8% of controls. The two groups differed significantly (P < 0.001) in asynapsed nuclei, fragmented SC and dotted SCs. In patients, asynapsis were short and limited to a few bivalents. Staging of pachytene nuclei based on the morphology of the XY pair with BRCA1 revealed a prevalence of early pachytene substages (70.7%) in patients. H2AX was normally phosphorylated.
CONCLUSIONS: In the absence of the AZFc region, the transient zygotene stage is extended, and chromosome condensation is reduced. The low level of limited asynapsis, the normal H2AX staining and the incomplete loss of germ cells at the pachytene checkpoint indicate that the AZFc region is not critical for meiotic recombination. We suggest that the pachytene phenotype develops secondarily to a primary defect that influences meiosis.
Key words: AZFc deletion/meiosis/asynapsis/SC fragmentation/pachytene checkpoint
Submitted on July 3, 2006; resubmitted on January 10, 2007; resubmitted on January 31, 2007; accepted on February 6, 2007.