Yuan Li, Liu Jian-Guo, Hoja Mary-Rose, Wilbertz Johannes, Nordqvist Katarina, Höög Christer
Center for Genomics and Bioinformatics and Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Science. 2002 May 10;296(5570):1115-8. doi: 10.1126/science.1070594.
Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss in humans and results from errors in meiotic chromosome segregation. Here, we show that the absence of synaptonemal complex protein 3 (SCP3) promotes aneuploidy in murine oocytes by inducing defective meiotic chromosome segregation. The abnormal oocyte karyotype is inherited by embryos, which die in utero at an early stage of development. In addition, embryo death in SCP3-deficient females increases with advancing maternal age. We found that SCP3 is required for chiasmata formation and for the structural integrity of meiotic chromosomes, suggesting that altered chromosomal structure triggers nondisjunction. SCP3 is thus linked to inherited aneuploidy in female germ cells and provides a model system for studying age-dependent degeneration in oocytes.
非整倍体（三体或单体）是人类妊娠丢失的主要遗传原因，由减数分裂染色体分离错误导致。在此，我们表明，联会复合体蛋白3（SCP3）的缺失通过诱导减数分裂染色体分离缺陷，促进小鼠卵母细胞发生非整倍体。异常的卵母细胞核型会遗传给胚胎，这些胚胎在子宫内发育早期死亡。此外，SCP3缺陷雌性小鼠中的胚胎死亡随着母龄增加而增多。我们发现，SCP3是交叉形成和减数分裂染色体结构完整性所必需的，这表明染色体结构改变引发了不分离。因此，SCP3与雌性生殖细胞中的遗传性非整倍体相关，并为研究卵母细胞中年龄依赖性退化提供了一个模型系统。
