Hunter Neil
Howard Hughes Medical Institute, University of California, Davis, Davis, California 95616.
Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, California 95616.
Cold Spring Harb Symp Quant Biol. 2017;82:235-247. doi: 10.1101/sqb.2017.82.035394. Epub 2018 May 9.
Oocyte quality and number are key determinants of reproductive life span and success. These variables are shaped in part by the elimination of oocytes that experience problems during the early stages of meiosis. Meiotic prophase-I marks an extended period of genome vulnerability in which epigenetic reprogramming unleashes retroelements and hundreds of DNA double-strand breaks (DSBs) are inflicted to initiate the programmed recombination required for accurate chromosome segregation at the first meiotic division. Expression of LINE-1 retroelements perturbs several aspects of meiotic prophase and is associated with oocyte death during the early stages of meiotic prophase I. Defects in chromosome synapsis and recombination also trigger oocyte loss, but typically at a later stage, as cells transition into quiescence and form primordial follicles. Interrelated pathways that signal defects in DSB repair and chromosome synapsis mediate this late oocyte attrition. Here, I review our current understanding of early and late oocyte attrition based on studies in mouse and describe how these processes appear to be both distinct and overlapping and how they help balance the quality and size of oocyte reserves to maximize fecundity.
卵母细胞的质量和数量是生殖寿命和成功率的关键决定因素。这些变量部分是由减数分裂早期出现问题的卵母细胞的清除所塑造的。减数分裂前期I标志着基因组易损性的延长时期，在此期间，表观遗传重编程释放逆转录元件，并造成数百个DNA双链断裂（DSB），以启动第一次减数分裂时准确染色体分离所需的程序性重组。LINE-1逆转录元件的表达扰乱了减数分裂前期的几个方面，并与减数分裂前期I早期的卵母细胞死亡有关。染色体联会和重组缺陷也会引发卵母细胞丢失，但通常在后期，当细胞进入静止状态并形成原始卵泡时。在DSB修复和染色体联会中发出缺陷信号的相互关联的途径介导了这种晚期卵母细胞损耗。在这里，我根据对小鼠的研究回顾了我们目前对早期和晚期卵母细胞损耗的理解，并描述了这些过程如何既不同又重叠，以及它们如何帮助平衡卵母细胞储备的质量和大小以最大化生育力。
