Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation.
Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation.
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DOI：
10.1371/journal.pone.0006186
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发表时间：
2009-07-09
期刊：
影响因子：
3.7
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Jagarlamudi K;Liu L;Adhikari D;Reddy P;Idahl A;Ottander U;Lundin E;Liu K
未成熟的卵巢原始卵泡对于维持雌性哺乳动物的生殖寿命是必不可少的。最近发现，在原始卵泡的卵母细胞中，编码磷脂酰肌醇3-激酶(PI3K)负调控因子PTEN的基因Pten(Pten，编码PI3K负性调节因子的基因)的缺失会导致原始卵泡中PI3K信号的过度激活，这表明卵母细胞中PI3K信号通路的激活对于控制卵泡的激活是重要的。为了研究PI3K信号在初级和进一步发育卵泡的卵母细胞中是否也在卵泡发育和排卵的后期发挥作用，我们通过表达透明带3(Zp3)启动子介导的Cre重组酶的转基因小鼠，从初级和进一步发育的卵泡的卵母细胞中条件性地删除了Pten基因。我们的结果表明，从初级和进一步发育的卵泡的卵母细胞中有效地删除了Pten，这表明主要的PI3K下游成分Akt的磷酸化水平升高。然而，卵泡发育没有改变，卵母细胞成熟也是正常的，这导致突变小鼠的生育能力正常，产仔大小没有改变。我们的数据表明，卵母细胞中适当调控的PTEN/PI3K-Akt信号对于控制原始卵泡的发育是必不可少的，而卵母细胞中PI3K信号的过度激活似乎并不影响卵泡的发育。这表明，在小鼠卵母细胞中，PTEN/PI3K信号具有控制卵泡激活的阶段特异性功能。
Immature ovarian primordial follicles are essential for maintenance of the reproductive lifespan of female mammals. Recently, it was found that overactivation of the phosphatidylinositol 3-kinase (PI3K) signaling in oocytes of primordial follicles by an oocyte-specific deletion of Pten (phosphatase and tensin homolog deleted on chromosome ten), the gene encoding PI3K negative regulator PTEN, results in premature activation of the entire pool of primordial follicles, indicating that activation of the PI3K pathway in oocytes is important for control of follicular activation. To investigate whether PI3K signaling in oocytes of primary and further developed follicles also plays a role at later stages in follicular development and ovulation, we conditionally deleted the Pten gene from oocytes of primary and further developed follicles by using transgenic mice expressing zona pellucida 3 (Zp3) promoter-mediated Cre recombinase. Our results show that Pten was efficiently deleted from oocytes of primary and further developed follicles, as indicated by the elevated phosphorylation of the major PI3K downstream component Akt. However, follicular development was not altered and oocyte maturation was also normal, which led to normal fertility with unaltered litter size in the mutant mice. Our data indicate that properly controlled PTEN/PI3K-Akt signaling in oocytes is essential for control of the development of primordial follicles whereas overactivation of PI3K signaling in oocytes does not appear to affect the development of growing follicles. This suggests that there is a stage-specific function of PTEN/PI3K signaling in mouse oocytes that controls follicular activation.
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