Jagarlamudi Krishna, Liu Lian, Adhikari Deepak, Reddy Pradeep, Idahl Annika, Ottander Ulrika, Lundin Eva, Liu Kui
Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
PLoS One. 2009 Jul 9;4(7):e6186. doi: 10.1371/journal.pone.0006186.
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.
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至关重要。最近发现，通过卵母细胞特异性缺失Pten（第10号染色体上缺失的磷酸酶和张力蛋白同源物），即编码PI3K负调节因子PTEN的基因，使原始卵泡卵母细胞中的磷脂酰肌醇3激酶（PI3K）信号过度激活，导致整个原始卵泡库过早激活，这表明卵母细胞中PI3K信号通路的激活对于卵泡激活的控制很重要。为了研究初级及进一步发育卵泡的卵母细胞中的PI3K信号在卵泡发育和排卵后期是否也起作用，我们利用表达透明带3（Zp3）启动子介导的Cre重组酶的转基因小鼠，有条件地从初级及进一步发育卵泡的卵母细胞中删除Pten基因。我们的结果表明，如PI3K主要下游成分Akt磷酸化水平升高所示，Pten已从初级及进一步发育卵泡的卵母细胞中有效删除。然而，卵泡发育未改变，卵母细胞成熟也正常，这导致突变小鼠生育能力正常，窝仔数未改变。我们的数据表明，卵母细胞中PTEN/PI3K-Akt信号的适当控制对于原始卵泡发育的控制至关重要，而卵母细胞中PI3K信号的过度激活似乎不影响生长卵泡的发育。这表明小鼠卵母细胞中PTEN/PI3K信号具有控制卵泡激活的阶段特异性功能。
