Reddy Pradeep, Liu Lian, Adhikari Deepak, Jagarlamudi Krishna, Rajareddy Singareddy, Shen Yan, Du Chun, Tang Wenli, Hämäläinen Tuula, Peng Stanford L, Lan Zi-Jian, Cooney Austin J, Huhtaniemi Ilpo, Liu Kui
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
Science. 2008 Feb 1;319(5863):611-3. doi: 10.1126/science.1152257.
In the mammalian ovary, progressive activation of primordial follicles from the dormant pool serves as the source of fertilizable ova. Menopause, or the end of female reproductive life, occurs when the primordial follicle pool is exhausted. However, the molecular mechanisms underlying follicle activation are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) in oocytes, a major negative regulator of phosphatidylinositol 3-kinase (PI3K), the entire primordial follicle pool becomes activated. Subsequently, all primordial follicles become depleted in early adulthood, causing premature ovarian failure (POF). Our results show that the mammalian oocyte serves as the headquarters of programming of follicle activation and that the oocyte PTEN-PI3K pathway governs follicle activation through control of initiation of oocyte growth.
在哺乳动物卵巢中，从静止库中逐渐激活原始卵泡是可受精卵子的来源。当原始卵泡库耗尽时，就会出现更年期，即女性生殖生命的结束。然而，卵泡激活背后的分子机制仍知之甚少。我们提供了遗传学证据，表明在卵母细胞中缺乏PTEN（第10号染色体缺失的磷酸酶和张力蛋白同源物）的小鼠中，磷脂酰肌醇3激酶（PI3K）的主要负调节因子，整个原始卵泡库被激活。随后，所有原始卵泡在成年早期耗尽，导致卵巢早衰（POF）。我们的结果表明，哺乳动物卵母细胞是卵泡激活编程的总部，卵母细胞PTEN-PI3K途径通过控制卵母细胞生长的启动来控制卵泡激活。
