Meiotic defects in a man with non-obstructive azoospermia: Case report
Meiotic defects in a man with non-obstructive azoospermia: Case report
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DOI：
10.1093/humrep/deh335
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发表时间：
2004-08-01
影响因子：
6.1
通讯作者：
Martin, RH
中科院分区：
文献类型：
--
作者：
Sun, F;Kozak, G;Martin, RH
不育男性的非整倍体精子频率增加。我们已经确定减少重组与人类非整倍体精子的产生有关。本研究的目的是确定某些不育病例是否与减数分裂重组减少有关。对一例33岁非梗阻性无精子症患者的减数分裂早期进行了分析。利用新近发展的免疫细胞遗传学技术对联会复合体（SC）进行了鉴定。减数分裂蛋白的抗体鉴定了SC（SYN 1/SCP 3）、着丝粒（CREST）和重组位点（MLH 1）。从不育男性中只回收了36个减数分裂扩散，而对照组中有数百个。三分之一的细胞处于偶线期，而对照组为4%，这表明二价体无法形成突触并进展到粗线期。不育男性的重组频率大大降低，平均仅为32.7 MLH 1灶/细胞（范围1-60），而对照供体为46.0（范围21-62）。高比例的细胞（73%）含有至少一个常染色体二价体，MLH 1病灶为零，而对照供体中仅为4.5%。SC中的不连续性也更普遍（68%的细胞vs 26%的对照）。这是第一次证明戏剧性的粗线期异常不育男子使用这些强大的新的免疫细胞遗传学技术。
Infertile men have an increased frequency of aneuploid sperm. We have determined that decreased recombination is associated with the production of aneuploid sperm in humans. The aim of this study was to determine whether some cases of infertility are associated with decreased meiotic recombination. Analysis of the early stages of meiosis was performed in a 33-year-old man with non-obstructive azoospermia. Newly developed immunocytogenetic techniques were used to identify the synaptonemal complex (SC) in various stages of prophase. Antibodies to meiotic proteins identified the SC (SYN1/SCP3), the centromere (CREST) and recombination sites (MLH1). Only 36 meiotic spreads were recovered from the infertile man, compared with hundreds available from controls. One-third of the cells were in zygotene compared with 4% in controls, demonstrating an inability of bivalents to synapse and progress to pachytene. The infertile man had a greatly reduced frequency of recombination, with a mean of only 32.7 MLH1 foci/cell (range 1-60) compared with 46.0 (range 21-62) in control donors. A high proportion of cells (73%) contained at least one autosomal bivalent with zero MLH1 foci, compared with only 4.5% in control donors. Discontinuities in the SC were also more prevalent (68% of cells versus 26% in controls). This is the first demonstration of dramatic pachytene-stage abnormalities in an infertile man using these powerful new immunocytogenetic techniques.