研究发现Cdk1分子对卵子发育成熟至关重要

2012-03-07 17:08 · wenmingw

瑞典的科学家在小鼠实验中发现,一种叫做Cdk1的分子对哺乳类生物卵子的发育成熟具有至关重要的作用,当缺乏该分子时,卵子将不能正常成熟。

导读:在到了生育年龄的女性中个,有一少部分人无法成功怀孕,即便是体外受精也无济于事,这是因为她们的卵子不能正常发育成熟……

女性的卵子如果不能发育成熟的话则不能成功怀孕,即便是体外受精(in vitro fertilization , IVF)也无济于事。现在,瑞典歌德堡大学的研究人员发现一种叫做Cdk1的分子对于哺乳类生物的卵子成熟具有十分重要的功能。将来,这项发现也许可以提高IVF的成功率。

在所有到了生育年龄的女性中有高达15%的人在为了成功怀孕而努力。IVF可以帮助这些女性成为妈妈。但是,即便是IVF也帮不到那些因为卵子不能正常发育成熟而无法怀孕的女性,因为为成熟的卵子时无法受精的。不过,由于歌德堡大学研究人员的这一发现,那些因为该原因而无法怀孕的女性可能会得到命运的改变。

“这是第一个功能性证据证实Cdk1是哺乳类生物卵子成熟的关键分子。如果该发现能转化到临床应用,这有可能提高IVF治疗的成功几率,帮助那些因为卵子不能成熟而无法怀孕的女人”化学与分子生物学院的Kui Liu教授说。

Kui Liu和他的同事在特异组织敲除的小鼠上开展研究实验。结果显示,当从小鼠的卵子中去除Cdk1分子后,卵子的成熟过程停止。当该分子被重新加入后,卵子则继续成熟过程。

Liu说:“我们希望能够在人类卵子中开展实验。该结果有希望在10年内得到临床应用。”


Cdk1, but not Cdk2, is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes

Deepak Adhikari, Wenjing Zheng, Yan Shen, Nagaraju Gorre, Guillaume Halet, Philipp Kaldis and Kui Liu

Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone (LH). The in vivo functional roles of cyclin-dependent kinases (Cdks) during resumption of meiosis in mammalian oocytes are largely unknown. Previous studies have shown that deletions of Cdk3, Cdk4, or Cdk6 in mice result in viable animals with normal oocyte maturation, indicating that these Cdks are not essential for the meiotic maturation of oocytes. In addition, conventional knockout of Cdk1 and Cdk2 leads to embryonic lethality and postnatal follicular depletion, respectively, making it impossible to study the functions of Cdk1 and Cdk2 in oocyte meiosis. In this study, we generated conditional knockout mice with oocyte-specific deletions of Cdk1 and Cdk2. We showed that the lack of Cdk1, but not of Cdk2, leads to female infertility due to a failure of resumption of meiosis in the oocyte. Re-introduction of Cdk1 mRNA into Cdk1-null oocytes largely resumed meiosis. Thus, Cdk1 is the sole Cdk that is essential and sufficient to drive resumption of meiosis in mouse oocytes. We also found that Cdk1 maintains the phosphorylation status of protein phosphatase 1 (PP1) and lamin A/C in oocytes in order for meiosis resumption to occur.

文献链接:https://hmg.oxfordjournals.org/content/early/2012/02/24/hmg.dds061.abstract

关键词: 发育 卵子 分子