Meiotic abnormalities in patients bearing complete AZFc deletion of Y chromosome.
BACKGROUND
We studied meiosis in three infertile patients presenting complete AZFc microdeletion and three controls.


METHODS
Primary spermatocytes were immunolabeled with SCP3, BRCA1 and gammaH2AX. 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.
Geoffroy-Siraudin
C
C
Laboratoire de Biologie de la Reproduction, Hôpital de la Conception, 147 Boulevard Baille, 13385 Marseille cedex 05, France.
Aknin-Seiffer
I
I
Metzler-Guillemain
C
C
Ghalamoun-Slaimi
R
R
Bonzi
M F
MF
Levy
R
R
Guichaoua
M R
MR
D000328:Adult; D019313:BRCA1 Protein / Q000032:analysis; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004268:DNA-Binding Proteins; D006657:Histones / Q000032:analysis; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000032:analysis; D049471:Pachytene Stage / Q000235:genetics; D012729:Sex Chromosome Aberrations; D013090:Spermatocytes / Q000737:chemistry / Q000473:pathology; D013737:Testis / Q000737:chemistry / Q000473:pathology
D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009687:Nuclear Proteins; C490060:SYCP3 protein, human