Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, CAS, Rumburska 89, 277 21 Libechov, Czech Republic.
Department of Cell Biology, Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Prague, Czech Republic.
Int J Mol Sci. 2018 Sep 19;19(9):2841. doi: 10.3390/ijms19092841.
The rate of chromosome segregation errors that emerge during meiosis I in the mammalian female germ line are known to increase with maternal age; however, little is known about the underlying molecular mechanism. The objective of this study was to analyze meiotic progression of mouse oocytes in relation to maternal age. Using the mouse as a model system, we analyzed the timing of nuclear envelope breakdown and the morphology of the nuclear lamina of oocytes obtained from young (2 months old) and aged females (12 months old). Oocytes obtained from older females display a significantly faster progression through meiosis I compared to the ones obtained from younger females. Furthermore, in oocytes from aged females, lamin A/C structures exhibit rapid phosphorylation and dissociation. Additionally, we also found an increased abundance of MPF components and increased translation of factors controlling translational activity in the oocytes of aged females. In conclusion, the elevated MPF activity observed in aged female oocytes affects precocious meiotic processes that can multifactorially contribute to chromosomal errors in meiosis I.
在哺乳动物雌性生殖系中减数分裂 I 过程中出现的染色体分离错误率随着母体年龄的增加而增加;然而,其潜在的分子机制知之甚少。本研究的目的是分析与母体年龄相关的小鼠卵母细胞减数分裂进程。使用小鼠作为模型系统,我们分析了核膜破裂的时间和从年轻(2 个月大)和年老(12 个月大)雌性获得的卵母细胞的核层形态。与从小龄雌性获得的卵母细胞相比,来自大龄雌性的卵母细胞在减数分裂 I 中表现出明显更快的进展。此外,在大龄雌性的卵母细胞中,层粘连蛋白 A/C 结构表现出快速磷酸化和解离。此外,我们还发现高龄雌性卵母细胞中 MPF 成分的丰度增加,以及控制翻译活性的因子的翻译增加。总之,在高龄雌性卵母细胞中观察到的升高的 MPF 活性影响早熟的减数分裂过程,这可能多因素导致减数分裂 I 中的染色体错误。