Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, United States of America.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, United States of America.
Semin Cell Dev Biol. 2018 Dec;84:90-99. doi: 10.1016/j.semcdb.2017.12.005. Epub 2017 Dec 26.
In virtually all sexually reproducing animals, oocytes arrest in meiotic prophase and resume meiosis in a conserved biological process called meiotic maturation. Meiotic arrest enables oocytes, which are amongst the largest cells in an organism, to grow and accumulate the necessary cellular constituents required to support embryonic development. Oocyte arrest can be maintained for a prolonged period, up to 50 years in humans, and defects in the meiotic maturation process interfere with the faithful segregation of meiotic chromosomes, representing the leading cause of human birth defects and female infertility. Hormonal signaling and interactions with somatic cells of the gonad control the timing of oocyte meiotic maturation. Signaling activates the CDK1/cyclin B kinase, which plays a central role in regulating the nuclear and cytoplasmic events of meiotic maturation. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation whereas cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is less well understood. Classically, meiotic maturation has been studied in organisms with large oocytes to facilitate biochemical analysis. Recently, the nematode Caenorhabditis elegans is emerging as a genetic paradigm for studying the regulation of oocyte meiotic maturation. Studies in this system have revealed conceptual, anatomical, and molecular links to oocytes in all animals including humans. This review focuses on the signaling mechanisms required to control oocyte growth and meiotic maturation in C. elegans and discusses how the downstream regulation of protein translation coordinates the completion of meiosis and the oocyte-to-embryo transition.
在几乎所有有性繁殖的动物中,卵母细胞在减数分裂前期停滞,并在一个称为减数分裂成熟的保守生物学过程中重新开始减数分裂。减数分裂停滞使卵母细胞(在生物体中是最大的细胞之一)能够生长并积累支持胚胎发育所需的必要细胞成分。卵母细胞的停滞可以维持很长时间,在人类中最长可达 50 年,减数分裂成熟过程中的缺陷会干扰减数分裂染色体的准确分离,这是导致人类出生缺陷和女性不孕的主要原因。激素信号和与性腺体细胞的相互作用控制卵母细胞减数分裂成熟的时间。信号激活 CDK1/周期蛋白 B 激酶,该激酶在调节减数分裂成熟的核和细胞质事件中发挥核心作用。核成熟包括核膜破裂、减数分裂纺锤体组装和染色体分离,而细胞质成熟涉及卵母细胞蛋白质翻译和细胞质细胞器的重大变化,对其了解较少。经典上,为了便于生化分析,在具有大卵母细胞的生物体中研究减数分裂成熟。最近,秀丽隐杆线虫作为研究卵母细胞减数分裂成熟调控的遗传范例正在兴起。该系统的研究揭示了包括人类在内的所有动物卵母细胞的概念、解剖和分子联系。本综述重点讨论了控制线虫卵母细胞生长和减数分裂成熟所需的信号机制,并讨论了蛋白质翻译的下游调节如何协调减数分裂的完成和卵母细胞到胚胎的转变。