Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients
Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients
复制标题
DOI：
10.1093/humrep/dep180
复制
发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Solari, A. J.
中科院分区：
文献类型：
--
作者：
Sciurano, R. B.;Luna Hisano, C. V.;Solari, A. J.
Klinefelter综合征是人类男性最常见的染色体异常。对11例经睾丸活检确诊为经典型非镶嵌型Klinefelter综合征的成年患者进行了研究，其中6例患者有生精灶，并对其周围支持细胞的性染色体构成进行了分析。活检的地形学研究表明，具有生殖细胞的小管是所有小管的一小部分（8-24%），尽管绝大多数没有生殖细胞。利用荧光原位杂交（FISH）技术，结合X-着丝粒探针和减数分裂蛋白的免疫定位，证明92个减数分裂精母细胞均为整倍体46，XY，能形成正常的单倍体配子。另一方面，支持细胞显示两个X染色体标记，即它们是47，XXY。这些结果为睾丸精子提取加ICSI程序应用于Klinefelter患者时的高成功率提供了理论基础。这也与先前在XXY小鼠模型中的研究一致。这些生精病灶很可能起源于随机丢失一条X染色体的精原细胞克隆，可能是在精原细胞有丝分裂活跃期发生的。
Klinefelter syndrome is the most frequent chromosome abnormality in human males. This paper aims to investigate the ploidy of meiotic and pre-meiotic germ cells found in spermatogenic foci, and furthermore, the sex chromosome constitution of Sertoli cells which surround these germ cells in non-mosaic Klinefelter patients.A survey of 11 adult patients diagnosed with classical, non-mosaic Klinefelter syndrome who underwent testicular biopsies, showed that six of them had spermatogenesis foci. The topographical study of the biopsies showed that tubuli with germ cells are a minor fraction (8-24%) of all tubuli, although the overwhelming majority is devoid of germ cells. Using fluorescence in situ hybridization (FISH) with probes for the X-centromere and immunolocalization of meiotic proteins, the present work shows that all the 92 meiotic spermatocytes analyzed with FISH were euploid, 46,XY, and thus can form normal, haploid gametes. On the other hand, Sertoli cells show two marks for the X chromosome, meaning that they are 47,XXY.These results provide a rationale for the high rate of success in the testicular sperm extraction plus ICSI procedures when applied to Klinefelter patients. It is also in agreement with previous studies in the XXY-mouse model. These spermatogenic foci most probably originate from clones of spermatogonia that have randomly lost one of the X chromosomes, probably during periods of life when high spermatogonial mitotic activity occurs.