Ferguson Kyle A, Chow Victor, Ma Sai
Department of Obstetrics and Gynaecology, Women's Hospital and Health Centre, University of British Columbia, Vancouver, Canada.
Hum Reprod. 2008 Apr;23(4):988-95. doi: 10.1093/humrep/den013. Epub 2008 Feb 12.
Male carriers of structural chromosomal abnormalities provide a useful model for studying the effects of impaired synapsis on human meioses and male fertility.
We used immunofluorescent techniques to examine recombination (MLH1), synapsis (SYCP3/SYCP1) and transcriptional inactivation (BRCA1/gammaH2AX/RNA polymerase II) of meiotic chromosomes in an azoospermic carrier of a t(8;13) reciprocal translocation. Two biopsies were performed 1 year apart and on different testes.
Global recombination rates differed between the two biopsies. Although global recombination rates were not altered when compared with control men, recombination frequencies were reduced specifically on the rearranged chromosomes. Asynapsed quadrivalents were observed in 90% and 87% of pachytene nuclei from the first and second biopsies, respectively, and were frequently associated with the sex chromosomes. BRCA1 and gammaH2AX, two proteins implicated in meiotic sex chromosome inactivation, localized along asynapsed regions regardless of whether or not they were associated with the sex chromosomes. Immunostaining for RNA polymerase II provided further evidence that unsynapsed regions are silenced during human meiosis.
The fidelity of synapsis is a critical factor in determining the outcome of gametogenesis in humans, as the transcriptional inactivation of asynapsed regions may silence meiotic genes, leading to meiotic arrest and infertility.
结构性染色体异常的男性携带者为研究联会受损对人类减数分裂及男性生育力的影响提供了一个有用的模型。
我们运用免疫荧光技术，对一名患有t(8;13)相互易位的无精子症携带者减数分裂染色体的重组（MLH1）、联会（SYCP3/SYCP1）及转录失活（BRCA1/γH2AX/RNA聚合酶II）进行检测。在相隔1年的时间里，对不同的睾丸进行了两次活检。
两次活检的整体重组率有所不同。尽管与对照男性相比整体重组率未发生改变，但重排染色体上的重组频率却显著降低。在第一次和第二次活检的粗线期细胞核中，分别有90%和87%观察到了未联会的四价体，且它们常与性染色体相关。参与减数分裂性染色体失活的两种蛋白BRCA1和γH2AX，无论是否与性染色体相关，均定位于未联会区域。RNA聚合酶II的免疫染色进一步证明，在人类减数分裂过程中未联会区域会发生沉默。
联会的准确性是决定人类配子发生结果的关键因素，因为未联会区域的转录失活可能会使减数分裂基因沉默，从而导致减数分裂停滞和不育。
