Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
J Hum Genet. 2012 Aug;57(8):515-22. doi: 10.1038/jhg.2012.61. Epub 2012 May 31.
The events that take place during the prophase of meiosis I are essential for the correct segregation of homologous chromosomes. Defects in these processes likely contribute to infertility or recurrent pregnancy loss in humans. To screen for candidate genes for reproductive failure due to meiotic defects, we have analyzed the gene expression patterns in fetal, neonatal and adult gonads of both male and female mice by microarray and thereby identified 241 genes that are expressed specifically during prophase of meiosis I. Combined with our previous data obtained from developing spermatocytes, a total of 99 genes were identified that are upregulated in early prophase I. We confirmed the meiotic prophase I-specific expression of these genes using qRT-PCR. To further screen this panel for candidate genes that fulfill important roles in homologous pairing, synapsis and recombination, we established a gene transfer system for prophase I oocytes in combination with in vitro organ culture of ovaries, and successfully determined the localization of the selected genes. This gene set can thus serve as a resource for targeted sequence analysis via next-generation sequencing to identify the genes associated with human reproduction failure due to meiotic defects.
减数分裂 I 前期发生的事件对于同源染色体的正确分离至关重要。这些过程中的缺陷可能导致人类不孕或反复妊娠丢失。为了筛选因减数分裂缺陷导致生殖失败的候选基因，我们通过微阵列分析了雌雄小鼠胎儿、新生儿和成年性腺中的基因表达模式，从而鉴定了 241 个在减数分裂 I 前期特异性表达的基因。结合我们之前从发育中的精母细胞获得的数据，总共鉴定出 99 个在早期减数分裂 I 中上调的基因。我们使用 qRT-PCR 证实了这些基因的减数分裂 I 前期特异性表达。为了进一步筛选这个面板中在同源配对、联会和重组中起重要作用的候选基因，我们建立了一个减数分裂 I 前期卵母细胞的基因转移系统，结合卵巢的体外器官培养，成功确定了所选基因的定位。因此，这个基因集可以作为通过下一代测序进行靶向序列分析的资源，以鉴定与减数分裂缺陷导致的人类生殖失败相关的基因。
