Department of Animal Science, Chungbuk National University, Cheong-Ju, Chungbuk, Republic of Korea.
Biol Reprod. 2018 Feb 1;98(2):153-161. doi: 10.1093/biolre/iox145.
In the final stage of oogenesis, mammalian oocytes generate a meiotic spindle and undergo chromosome segregation to yield an egg that is ready for fertilization. Herein, we describe the recent advances in understanding the mechanisms controlling formation of the meiotic spindle in metaphase I (MI) and metaphase II (MII) in mammalian oocytes, and focus on the differences between mouse and human oocytes. Unlike mitotic cells, mammalian oocytes lack typical centrosomes that consist of two centrioles and the surrounding pericentriolar matrix proteins, which serve as microtubule-organizing centers (MTOCs) in most somatic cells. Instead, oocytes rely on different mechanisms for the formation of microtubules in MI spindles. Two different mechanisms have been described for MI spindle formation in mammalian oocytes. Chromosome-mediated microtubule formation, including RAN-mediated spindle formation and chromosomal passenger complex-mediated spindle elongation, controls the growth of microtubules from chromatin, while acentriolar MTOC-mediated microtubule formation contributes to spindle formation. Mouse oocytes utilize both chromatin- and MTOC-mediated pathways for microtubule formation. The existence of both pathways may provide a fail-safe mechanism to ensure high fidelity of chromosome segregation during meiosis. Unlike mouse oocytes, human oocytes considered unsuitable for clinical in vitro fertilization procedures, lack MTOCs; this may explain why meiosis in human oocytes is often error-prone. Understanding the mechanisms of MI/MII spindle formation, spindle assembly checkpoint, and chromosome segregation, in mammalian oocytes, will provide valuable insights into the molecular mechanisms of human infertility.
在卵母细胞的减数分裂末期,哺乳动物卵母细胞生成一个减数分裂纺锤体并进行染色体分离,产生一个准备受精的卵子。本文描述了近年来对控制哺乳动物卵母细胞中期 I (MI) 和中期 II (MII) 减数分裂纺锤体形成机制的理解的最新进展,并重点关注了小鼠和人类卵母细胞之间的差异。与有丝分裂细胞不同,哺乳动物卵母细胞缺乏由两个中心体和周围的中心体周围基质蛋白组成的典型中心体,而中心体是大多数体细胞中的微管组织中心 (MTOC)。相反,卵母细胞依赖于不同的机制来形成 MI 纺锤体中的微管。已经描述了两种不同的机制来形成哺乳动物卵母细胞中的 MI 纺锤体。染色体介导的微管形成,包括 RAN 介导的纺锤体形成和染色体乘客复合物介导的纺锤体伸长,控制着从染色质生长的微管,而无中心体的 MTOC 介导的微管形成有助于纺锤体的形成。小鼠卵母细胞利用染色质和 MTOC 介导的途径来形成微管。这两种途径的存在可能提供了一种故障安全机制,以确保减数分裂过程中染色体分离的高度保真度。与小鼠卵母细胞不同,被认为不适合临床体外受精程序的人类卵母细胞缺乏 MTOC;这可能解释了为什么人类卵母细胞的减数分裂经常容易出错。了解哺乳动物卵母细胞中的 MI/MII 纺锤体形成、纺锤体组装检查点和染色体分离的机制,将为理解人类不育症的分子机制提供有价值的见解。