image: Mechanistic model for MTOC maturation in GV oocytes. The MTOC (grey) activates near the oocyte cortex, which requires recruitment of CKAP5 and TACC3. After activation, MTOC migrates to the nuclear envelope, facilitated by dynein/dynactin. Disrupted MTOC maturation is associated with advanced maternal aging.
Credit: ©Science China Press
Human reproduction starts when an egg is fertilized by a sperm. Oocytes mature into eggs following the first meiosis, which is dependent on the meiotic spindle. Different from somatic cells, where centrosomes play a pivotal role in spindle assembly, oocytes eliminate centrosomes before maturation. Instead, the spindle is organized by microtubule organizing centers (MTOCs) in mammalian oocytes, such as human and mouse. MTOCs-mediated spindle assembly is an intricate process, requiring various sequential events. As early as prophase, oocytes set about making preparations for spindle assembly, but the details remain unclear.
Recently, a study from Lei Wang, Qing Sang, and Tianyu Wu’s lab in Fudan University systematically describes the dynamics of MTOCs in human and mouse GV oocytes, and dissects the mechanisms underlying MTOCs maturation, a process defined by the researchers. Importantly, the physiological and pathological significances of MTOCs maturation are also explored in this article.
In detail, MTOCs maturation comprises two tightly coupled processes referred to as MTOCs activation and MTOCs migration. At the very beginning, MTOCs remain quiescent under the cortex. As meiosis resumes, MTOCs begin to expand and gradually form astral microtubules, which is called MTOCs activation. Shortly after activation, MTOCs relocate to the nuclear periphery, called MTOCs migration. Furthermore, investigators performed high-resolution imaging of dozens of proteins to uncover the MTOCs components in GV oocytes. Based on the map, they try to screen out the key factors participating in MTOCs maturation. By stepwise investigations, they successfully reveal that CKAP5 and TACC3 are required in MTOCs activation, while MTOCs migration relies on the dynein/dynactin complex. The article also provides details on how these proteins are recruited to MTOCs and how they are modified to properly function in this process.
By comparing MTOCs maturation in human and mouse oocytes, a conclusion can be reached that not only is the process of maturation largely similar, but the key factors of MTOC maturation are also shared in human and mouse oocytes, implying that MTOCs maturation is largely conserved in mammalian oocytes. The interesting findings drop a hint that after centrosome loss, oocytes may evolve a common pathway to prepare for spindle assembly.
The physiological significance of MTOCs maturation is also discussed in this article. Considering the facts that disruption of MTOCs maturation results in spindle assembly failure and reduced oocyte maturation, MTOCs maturation is a prerequisite for spindle assembly in oocytes, which further expands our understanding of MTOCs-mediated spindle assembly in oocytes.
It is known that advanced maternal age correlates with reduced female fertility. With the increased childbearing age, oocyte aging-related female infertility is becoming an urgent public health issue worldwide. Here, the researchers report that MTOC maturation is greatly impaired in aged human oocytes (women aged >35 years old) compared with young human oocytes (women aged ≤35 years old), which is likely explained by the reduced CKAP5 accumulation on MTOCs. The findings in this article help to deepen our knowledge of oocyte aging.
Journal
Science Bulletin